10-7964835-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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. 14/20 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 Likely benign in UniProt.

• 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

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

Verdict is Benign. Variant got -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

GnomAD3 exomes AF: 0.617 AC: 153701 AN: 249222 Hom.: 48763 AF XY: 0.611 AC XY: 82690 AN XY: 135248

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 SAS exome AF: 0.554

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

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.764

Gnomad4 ASJ exome AF: 0.667

Gnomad4 EAS exome AF: 0.741

Gnomad4 SAS exome AF: 0.559

Gnomad4 FIN exome AF: 0.645

Gnomad4 NFE exome AF: 0.592

Gnomad4 OTH exome AF: 0.580

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

Gnomad4 AFR AF: 0.327

Gnomad4 AMR AF: 0.678

Gnomad4 ASJ AF: 0.661

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.553

Gnomad4 FIN AF: 0.657

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.562

Alfa AF: 0.590 Hom.: 68942

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
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

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