10-7965597-T-G

Variant names:

• chr10-7965597-T-G
• rs1244229
• NM_031923.4:c.2087T>G

Variant summary

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

The NM_031923.4(TAF3):​c.2087T>G​(p.Val696Gly) 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. 14/21 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. V696A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 26)
• Consequence: TAF3 NM_031923.4 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 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=0.05201751).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF3	NM_031923.4	c.2087T>G	p.Val696Gly	missense_variant	Exon 3 of 7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.2084T>G	p.Val695Gly	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.2087T>G	p.Val696Gly	missense_variant	Exon 3 of 7	1	NM_031923.4	ENSP00000340271.5

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 53

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	20
DANN	Benign	0.91
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.18	T
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.34	N
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.17
Sift	Benign	0.083	T
Sift4G	Benign	0.26	T
Polyphen		0.0	B
Vest4		0.15
MutPred		0.10		Loss of stability (P = 0.0408);
MVP		0.068
MPC		0.26
ClinPred		0.18	T
GERP RS		5.8
Varity_R		0.083
gMVP		0.020

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;