6-34882973-C-G

Variant names:

• chr6-34882973-C-G
• rs202203012
• NM_005643.4:c.279G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005643.4(TAF11):​c.279G>C​(p.Glu93Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,608,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TAF11 NM_005643.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.777

Genes affected

TAF11 (HGNC:11544): (TATA-box binding protein associated factor 11) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes a small subunit of TFIID that is present in all TFIID complexes and interacts with TBP. This subunit also interacts with another small subunit, TAF13, to form a heterodimer with a structure similar to the histone core structure. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2012]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10079551).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF11	NM_005643.4	c.279G>C	p.Glu93Asp	missense_variant	Exon 2 of 5	ENST00000361288.9	NP_005634.1
TAF11	NM_001270488.1	c.279G>C	p.Glu93Asp	missense_variant	Exon 2 of 4		NP_001257417.1
TAF11	XM_011514827.3	c.147G>C	p.Glu49Asp	missense_variant	Exon 2 of 5		XP_011513129.1
TAF11	XM_047419270.1	c.147G>C	p.Glu49Asp	missense_variant	Exon 2 of 4		XP_047275226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF11	ENST00000361288.9	c.279G>C	p.Glu93Asp	missense_variant	Exon 2 of 5	1	NM_005643.4	ENSP00000354633.4

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000275 AC: 4 AN: 1456748 Hom.: 0 Cov.: 31 AF XY: 0.00000276 AC XY: 2 AN XY: 724326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152166 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74320

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.025	.;.;T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.10	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.1	.;M;M
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.6	.;N;N
REVEL	Benign	0.030
Sift	Benign	0.13	.;T;T
Sift4G	Benign	0.10	.;T;T
Polyphen		0.15	.;.;B
Vest4		0.21, 0.17
MutPred		0.23		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.54
MPC		0.53
ClinPred		0.59	D
GERP RS		2.4
Varity_R		0.30
gMVP		0.15

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs202203012; hg19: chr6-34850750;