6-34883357-T-C

Variant names:

• chr6-34883357-T-C
• rs2273006
• NM_005643.4:c.172-277A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005643.4(TAF11):​c.172-277A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 150,340 control chromosomes in the GnomAD database, including 9,904 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (9904 hom., cov: 31)
• Consequence: TAF11 NM_005643.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 9 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF11	NM_005643.4	c.172-277A>G		intron_variant	Intron 1 of 4	ENST00000361288.9	NP_005634.1
TAF11	NM_001270488.1	c.172-277A>G		intron_variant	Intron 1 of 3		NP_001257417.1
TAF11	XM_011514827.3	c.39+42A>G		intron_variant	Intron 1 of 4		XP_011513129.1
TAF11	XM_047419270.1	c.39+42A>G		intron_variant	Intron 1 of 3		XP_047275226.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF11	ENST00000361288.9	c.172-277A>G		intron_variant	Intron 1 of 4	1	NM_005643.4	ENSP00000354633.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46488 AN: 150222 Hom.: 9883 Cov.: 31

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.271

Gnomad ASJ AF: 0.295

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.293

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.322

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.310 AC: 46553 AN: 150340 Hom.: 9904 Cov.: 31 AF XY: 0.310 AC XY: 22739 AN XY: 73450

African (AFR) AF: 0.596 AC: 23989 AN: 40226

American (AMR) AF: 0.271 AC: 4100 AN: 15136

Ashkenazi Jewish (ASJ) AF: 0.295 AC: 1016 AN: 3440

East Asian (EAS) AF: 0.580 AC: 2963 AN: 5112

South Asian (SAS) AF: 0.310 AC: 1480 AN: 4774

European-Finnish (FIN) AF: 0.146 AC: 1548 AN: 10570

Middle Eastern (MID) AF: 0.291 AC: 85 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10599 AN: 67810

Other (OTH) AF: 0.321 AC: 666 AN: 2076

Alfa AF: 0.195 Hom.: 2725

Bravo AF: 0.330

Asia WGS AF: 0.415 AC: 1444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2273006; hg19: chr6-34851134;