SMARCD1

Chr 12AD

SWI/SNF related BAF chromatin remodeling complex subunit D1

Also known as: BAF60A, CRACD1, CSS11, Rsc6p

NCBI Gene: 6602 ENSG00000066117 UniProt: Q96GM5 OMIM: 601735

The encoded protein is a component of the SWI/SNF chromatin remodeling complex that uses ATP-dependent mechanisms to alter chromatin structure and regulate gene transcription. Heterozygous loss-of-function mutations cause Coffin-Siris syndrome 11, an autosomal dominant disorder characterized by developmental delay, intellectual disability, and distinctive facial features. The high constraint scores (pLI 0.999, LOEUF 0.206) indicate the gene is highly intolerant to loss-of-function variants, consistent with haploinsufficiency as the disease mechanism.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 has sequence similarity to the yeast Swp73 protein. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

GeneReviews OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.211 OMIM phenotype

Clinical Summary— SMARCD1

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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

9 unique Pathogenic / Likely Pathogenic· 87 VUS of 128 total submissions

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GeneReview available — SMARCD1

Authoritative clinical overview · Recommended first read

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.21LOEUF

pLI 0.999

Z-score 4.78

OE 0.07 (0.03–0.21)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?

3.44Z-score

OE missense 0.42 (0.36–0.49)

117 obs / 278.7 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.07 (0.03–0.21)

0≤0.351.4

Missense OE?0.42 (0.36–0.49)

0≤0.61.4

Synonymous OE?0.88

0≤1.21.6

LoF obs/exp: 2 / 30.5Missense obs/exp: 117 / 278.7Syn Z: 0.90

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

moderateSMARCD1-related syndromic intellectual disabilityOTHERAD

This gene — mechanism propensity

0.4090th %ile

GOF

0.2298th %ile

LOF

0.81top 5%

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

LOFprediction above median · 33% of P/LP variants are LoF · LOEUF 0.21

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

128 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic2

VUS87

Likely Benign11

Benign9

Conflicting1

Pathogenic

Likely Pathogenic

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	3	4	0	0	7
Likely Pathogenic	0	2	0	0	2
VUS	7	79	1	0	87
Likely Benign	0	4	3	4	11
Benign	0	1	8	0	9
Conflicting	—				1
Total	10	90	12	4	117

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

View in ClinVar →

4 pathogenic / likely-pathogenic (of 6) ClinVar copy-number / structural variants overlap SMARCD1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →