10-7965597-T-C

Position:

• chr10-7965597-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000344293.6(TAF3):​c.2087T>C​(p.Val696Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.707 in 1,588,220 control chromosomes in the GnomAD database, including 398,234 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V696L) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.70 (35776 hom., cov: 26)
  • Exomes 𝑓: 0.71 (362458 hom.)
• Consequence: TAF3 ENST00000344293.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.41

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=6.45388E-7).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF3	NM_031923.4	c.2087T>C	p.Val696Ala	missense_variant	3/7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.2084T>C	p.Val695Ala	missense_variant	3/7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6	c.2087T>C	p.Val696Ala	missense_variant	3/7	1	NM_031923.4	ENSP00000340271	P4

Frequencies

GnomAD3 genomes AF: 0.699 AC: 103293 AN: 147826 Hom.: 35753 Cov.: 26

Gnomad AFR AF: 0.614

Gnomad AMI AF: 0.749

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.810

Gnomad EAS AF: 0.725

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.747

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.727

GnomAD3 exomes AF: 0.726 AC: 170323 AN: 234536 Hom.: 62333 AF XY: 0.726 AC XY: 92686 AN XY: 127682

Gnomad AFR exome AF: 0.591

Gnomad AMR exome AF: 0.830

Gnomad ASJ exome AF: 0.800

Gnomad EAS exome AF: 0.715

Gnomad SAS exome AF: 0.745

Gnomad FIN exome AF: 0.727

Gnomad NFE exome AF: 0.706

Gnomad OTH exome AF: 0.736

GnomAD4 exome AF: 0.708 AC: 1020292 AN: 1440286 Hom.: 362458 Cov.: 53 AF XY: 0.710 AC XY: 508506 AN XY: 715940

Gnomad4 AFR exome AF: 0.595

Gnomad4 AMR exome AF: 0.824

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.760

Gnomad4 SAS exome AF: 0.751

Gnomad4 FIN exome AF: 0.724

Gnomad4 NFE exome AF: 0.699

Gnomad4 OTH exome AF: 0.703

GnomAD4 genome AF: 0.699 AC: 103352 AN: 147934 Hom.: 35776 Cov.: 26 AF XY: 0.705 AC XY: 50802 AN XY: 72026

Gnomad4 AFR AF: 0.614

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.810

Gnomad4 EAS AF: 0.725

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.747

Gnomad4 NFE AF: 0.709

Gnomad4 OTH AF: 0.725

Alfa AF: 0.707 Hom.: 58534

Bravo AF: 0.686

TwinsUK AF: 0.689 AC: 2554

ALSPAC AF: 0.687 AC: 2649

ESP6500AA AF: 0.601 AC: 2218

ESP6500EA AF: 0.712 AC: 5817

ExAC AF: 0.722 AC: 87263

Asia WGS AF: 0.672 AC: 2340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	19
DANN	Benign	0.84
DEOGEN2	Benign	0.0079	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	6.5e-7	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	P
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.28	N
REVEL	Benign	0.19
Sift	Benign	0.19	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.24
ClinPred		0.0091	T
GERP RS		5.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.036
gMVP		0.018

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: rs1244229; hg19: chr10-8007560; COSMIC: COSV60207032;