NM_031923.4:c.1000C>G

Variant names:

• chr10-7964510-C-G
• rs773266356
• NM_031923.4:c.1000C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031923.4(TAF3):​c.1000C>G​(p.Pro334Ala) 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. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF3 NM_031923.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.13

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08839685).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF3	NM_031923.4	c.1000C>G	p.Pro334Ala	missense_variant	Exon 3 of 7	ENST00000344293.6	NP_114129.1
TAF3	XM_011519741.2	c.997C>G	p.Pro333Ala	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.1000C>G	p.Pro334Ala	missense_variant	Exon 3 of 7	1	NM_031923.4	ENSP00000340271.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000407 AC: 1 AN: 245508 Hom.: 0 AF XY: 0.00000749 AC XY: 1 AN XY: 133532

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000329

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000828 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	9.9
DANN	Benign	0.56
DEOGEN2	Benign	0.017	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Benign	0.37	T
Sift4G	Benign	0.41	T
Polyphen		0.0	B
Vest4		0.097
MutPred		0.19		Gain of MoRF binding (P = 0.0444);
MVP		0.14
MPC		0.21
ClinPred		0.053	T
GERP RS		4.5
Varity_R		0.038
gMVP		0.054

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: rs773266356; hg19: chr10-8006473;