TAF1C

Chr 16

TATA-box binding protein associated factor, RNA polymerase I subunit C

Also known as: MGC:39976, SL1, TAFI110, TAFI95

NCBI Gene: 9013 ENSG00000103168 UniProt: Q15572 OMIM: 604905

TAF1C encodes a component of the SL1/TIF-IB transcription factor complex that is essential for RNA polymerase I-dependent transcription of ribosomal RNA genes and formation of the pre-initiation complex. Mutations cause intellectual disability with language impairment and with or without autistic features, following an autosomal dominant inheritance pattern. This gene shows moderate constraint against loss-of-function variants, and the associated neurodevelopmental phenotype typically manifests in early childhood.

OMIM ResearchSummary from RefSeq, UniProt

Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2011]

OMIM ResearchGenerating clinical summary…

LOEUF 1.29

Clinical Summary— TAF1C

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

3 unique Pathogenic / Likely Pathogenic· 204 VUS of 267 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.29LOEUF

pLI 0.000

Z-score 0.11

OE 0.98 (0.75–1.29)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-2.29Z-score

OE missense 1.28 (1.20–1.36)

684 obs / 534.7 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.98 (0.75–1.29)

0≤0.351.4

Missense OE?1.28 (1.20–1.36)

0≤0.61.4

Synonymous OE?1.32

0≤1.21.6

LoF obs/exp: 37 / 37.7Missense obs/exp: 684 / 534.7Syn Z: -3.89

ClinVar Variant Classifications

267 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

VUS204

Likely Benign26

Benign7

Conflicting1

Pathogenic

204

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	3	0	3
Likely Pathogenic	0	0	0	0	0
VUS	3	200	1	0	204
Likely Benign	0	20	2	4	26
Benign	0	2	3	2	7
Conflicting	—				1
Total	3	222	9	6	241

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

View in ClinVar →

45 pathogenic / likely-pathogenic (of 76) ClinVar copy-number / structural variants overlap TAF1C — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →