Variant rs17366712 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_031923.4(TAF3):c.1046G>C(p.Ser349Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0435 in 1,613,814 control chromosomes in the GnomAD database, including 1,730 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.032 ( 105 hom., cov: 32)

Exomes 𝑓: 0.045 ( 1625 hom. )

Consequence

TAF3
NM_031923.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.81

Variant links:

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]

TAF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026902258).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0322 (4896/152144) while in subpopulation NFE AF= 0.0461 (3133/67984). AF 95% confidence interval is 0.0447. There are 105 homozygotes in gnomad4. There are 2371 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4896 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF3	NM_031923.4 link	c.1046G>C	p.Ser349Thr	missense_variant	Exon 3 of 7	ENST00000344293.6	NP_114129.1	Q5VWG9
TAF3	XM_011519741.2 link	c.1043G>C	p.Ser348Thr	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 link	c.1046G>C	p.Ser349Thr	missense_variant	Exon 3 of 7	1	NM_031923.4	ENSP00000340271.5		Q5VWG9

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4897

AN:

152026

Hom.:

105

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00860

Gnomad AMI

AF:

0.0318

Gnomad AMR

AF:

0.0333

Gnomad ASJ

AF:

0.0248

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.0215

Gnomad FIN

AF:

0.0575

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0461

Gnomad OTH

AF:

0.0307

GnomAD3 exomes

AF:

0.0366

AC:

9089

AN:

248252

Hom.:

204

AF XY:

0.0363

AC XY:

4887

AN XY:

134766

show subpopulations

Gnomad AFR exome

AF:

0.00813

Gnomad AMR exome

AF:

0.0422

Gnomad ASJ exome

AF:

0.0251

Gnomad EAS exome

AF:

0.000224

Gnomad SAS exome

AF:

0.0276

Gnomad FIN exome

AF:

0.0555

Gnomad NFE exome

AF:

0.0446

Gnomad OTH exome

AF:

0.0327

GnomAD4 exome

AF:

0.0447

AC:

65360

AN:

1461670

Hom.:

1625

Cov.:

AF XY:

0.0439

AC XY:

31888

AN XY:

727110

show subpopulations

Gnomad4 AFR exome

AF:

0.00729

Gnomad4 AMR exome

AF:

0.0409

Gnomad4 ASJ exome

AF:

0.0248

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0278

Gnomad4 FIN exome

AF:

0.0517

Gnomad4 NFE exome

AF:

0.0495

Gnomad4 OTH exome

AF:

0.0383

GnomAD4 genome

AF:

0.0322

AC:

4896

AN:

152144

Hom.:

105

Cov.:

AF XY:

0.0319

AC XY:

2371

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.00857

Gnomad4 AMR

AF:

0.0334

Gnomad4 ASJ

AF:

0.0248

Gnomad4 EAS

AF:

0.000580

Gnomad4 SAS

AF:

0.0216

Gnomad4 FIN

AF:

0.0575

Gnomad4 NFE

AF:

0.0461

Gnomad4 OTH

AF:

0.0303

Alfa

AF:

0.0376

Hom.:

Bravo

AF:

0.0296

TwinsUK

AF:

0.0529

AC:

196

ALSPAC

AF:

0.0529

AC:

204

ESP6500AA

AF:

0.00778

AC:

ESP6500EA

AF:

0.0449

AC:

368

ExAC

AF:

0.0353

AC:

4261

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.032

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0027

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.90

REVEL

Benign

0.13

Sift

Benign

0.037

Sift4G

Benign

0.57

Polyphen

0.18

Vest4

0.050

MPC

0.47

ClinPred

0.020

GERP RS

3.5

Varity_R

0.037

gMVP

0.17

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over