chr10-7964835-A-G

Variant names:

• chr10-7964835-A-G
• rs4747647
• NM_031923.4:c.1325A>G

Variant summary

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

The NM_031923.4(TAF3):​c.1325A>G​(p.Asn442Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.59 in 1,613,814 control chromosomes in the GnomAD database, including 286,106 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. N442Y) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.54 (23438 hom., cov: 31)
  • Exomes 𝑓: 0.60 (262668 hom.)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159
• Publications: 29 publications found

Genes affected

TAF3 (HGNC:17303): (TATA-box binding protein associated factor 3) The highly conserved RNA polymerase II transcription factor TFIID (see TAF1; MIM 313650) comprises the TATA box-binding protein (TBP; MIM 600075) and a set of TBP-associated factors (TAFs), including TAF3. TAFs contribute to promoter recognition and selectivity and act as antiapoptotic factors (Gangloff et al., 2001 [PubMed 11438666]).[supplied by OMIM, May 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.2375051E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF3	NM_031923.4	c.1325A>G	p.Asn442Ser	missense_variant	Exon 3 of 7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.1322A>G	p.Asn441Ser	missense_variant	Exon 3 of 7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6	c.1325A>G	p.Asn442Ser	missense_variant	Exon 3 of 7	1	NM_031923.4	ENSP00000340271.5

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81749 AN: 151846 Hom.: 23434 Cov.: 31

Gnomad AFR AF: 0.327

Gnomad AMI AF: 0.672

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.661

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.633

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.565

GnomAD2 exomes AF: 0.617 AC: 153701 AN: 249222 AF XY: 0.611

Gnomad AFR exome AF: 0.325

Gnomad AMR exome AF: 0.775

Gnomad ASJ exome AF: 0.665

Gnomad EAS exome AF: 0.702

Gnomad FIN exome AF: 0.651

Gnomad NFE exome AF: 0.600

Gnomad OTH exome AF: 0.628

GnomAD4 exome AF: 0.596 AC: 870841 AN: 1461848 Hom.: 262668 Cov.: 77 AF XY: 0.595 AC XY: 432732 AN XY: 727226

African (AFR) AF: 0.313 AC: 10485 AN: 33478

American (AMR) AF: 0.764 AC: 34152 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 17426 AN: 26132

East Asian (EAS) AF: 0.741 AC: 29425 AN: 39698

South Asian (SAS) AF: 0.559 AC: 48190 AN: 86258

European-Finnish (FIN) AF: 0.645 AC: 34433 AN: 53402

Middle Eastern (MID) AF: 0.583 AC: 3363 AN: 5768

European-Non Finnish (NFE) AF: 0.592 AC: 658332 AN: 1111992

Other (OTH) AF: 0.580 AC: 35035 AN: 60396

GnomAD4 genome AF: 0.538 AC: 81780 AN: 151966 Hom.: 23438 Cov.: 31 AF XY: 0.547 AC XY: 40604 AN XY: 74260

African (AFR) AF: 0.327 AC: 13556 AN: 41424

American (AMR) AF: 0.678 AC: 10365 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.661 AC: 2294 AN: 3468

East Asian (EAS) AF: 0.704 AC: 3630 AN: 5154

South Asian (SAS) AF: 0.553 AC: 2659 AN: 4808

European-Finnish (FIN) AF: 0.657 AC: 6942 AN: 10572

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.594 AC: 40358 AN: 67946

Other (OTH) AF: 0.562 AC: 1177 AN: 2094

Alfa AF: 0.579 Hom.: 102142

Bravo AF: 0.533

TwinsUK AF: 0.584 AC: 2165

ALSPAC AF: 0.587 AC: 2264

ESP6500AA AF: 0.358 AC: 1374

ESP6500EA AF: 0.609 AC: 5028

ExAC AF: 0.604 AC: 72954

Asia WGS AF: 0.560 AC: 1948 AN: 3478

EpiCase AF: 0.595

EpiControl AF: 0.606

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.059
BayesDel_addAF	Benign	-0.82	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.041
DANN	Benign	0.82
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.73	T
MetaRNN	Benign	0.0000012	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.16
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.089
Sift	Benign	0.32	T
Sift4G	Benign	0.47	T
Polyphen		0.0030	B
Vest4		0.013
MPC		0.16
ClinPred		0.0037	T
GERP RS		1.7
Varity_R		0.014
gMVP		0.094
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4747647; hg19: chr10-8006798; COSMIC: COSV60205848;