SMARCC1

Chr 3AD

SWI/SNF related BAF chromatin remodeling complex subunit C1

Also known as: BAF155, CRACC1, HYC5, Rsc8, SRG3, SWI3

NCBI Gene: 6599 ENSG00000173473 UniProt: Q92922 OMIM: 601732

SMARCC1 encodes a component of SWI/SNF chromatin remodeling complexes that alters chromatin structure in an ATP-dependent manner and is essential for neural stem cell proliferation and neuronal differentiation. Mutations cause autosomal dominant congenital hydrocephalus with susceptibility to this condition. The gene is highly constrained against loss-of-function variants (pLI >0.99), reflecting its critical role in neurodevelopment.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and contains a predicted leucine zipper motif typical of many transcription factors. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.121 OMIM phenotype

Clinical Summary— SMARCC1

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Gene-Disease Validity (ClinGen)

SMARCC1-associated developmental dysgenesis syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

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ClinVar Variants

10 unique Pathogenic / Likely Pathogenic· 157 VUS of 233 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

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GeneReview available — SMARCC1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?

0.12LOEUF

pLI 1.000

Z-score 7.23

OE 0.04 (0.02–0.12)

Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?

2.45Z-score

OE missense 0.72 (0.67–0.78)

438 obs / 607.7 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.04 (0.02–0.12)

0≤0.351.4

Missense OE?0.72 (0.67–0.78)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 3 / 66.7Missense obs/exp: 438 / 607.7Syn Z: 0.24

This gene — mechanism propensity

0.2698th %ile

GOF

0.2796th %ile

LOF

0.82top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 90% of P/LP variants are LoF · LOEUF 0.12

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

233 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2

Likely Pathogenic8

VUS157

Likely Benign21

Benign3

Conflicting2

Pathogenic

Likely Pathogenic

157

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	2	0	0	0	2
Likely Pathogenic	7	1	0	0	8
VUS	12	141	4	0	157
Likely Benign	0	7	5	9	21
Benign	0	2	0	1	3
Conflicting	—				2
Total	21	151	9	10	193

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

7 pathogenic / likely-pathogenic (of 12) ClinVar copy-number / structural variants overlap SMARCC1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →