6-34887932-G-C

Position:

• chr6-34887932-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005643.4(TAF11):​c.26C>G​(p.Ser9Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF11 NM_005643.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.787

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060072124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF11	NM_005643.4	c.26C>G	p.Ser9Cys	missense_variant	1/5	ENST00000361288.9
TAF11	NM_001270488.1	c.26C>G	p.Ser9Cys	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF11	ENST00000361288.9	c.26C>G	p.Ser9Cys	missense_variant	1/5	1	NM_005643.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 19, 2024

The c.26C>G (p.S9C) alteration is located in exon 1 (coding exon 1) of the TAF11 gene. This alteration results from a C to G substitution at nucleotide position 26, causing the serine (S) at amino acid position 9 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.087
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	20
DANN	Benign	0.90
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.082	N
LIST_S2	Benign	0.48	T;T;T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.060	T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
Polyphen		0.042	.;.;B
Vest4		0.15, 0.15
MutPred		0.14		Loss of phosphorylation at S9 (P = 0.006);Loss of phosphorylation at S9 (P = 0.006);Loss of phosphorylation at S9 (P = 0.006);
MVP		0.28
MPC		0.64
ClinPred		0.11	T
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.15
gMVP		0.097

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: rs1263291235; hg19: chr6-34855709; COSMIC: COSV63543250; COSMIC: COSV63543250;