Variant 10-7964606-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031923.4(TAF3):c.1096C>A(p.Pro366Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000486 in 1,461,872 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000049 ( 2 hom. )

Consequence

TAF3
NM_031923.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.54

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:

TAF3 (HGNC:):

TAF3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.039312303).

BS2

High AC in GnomAdExome4 at 71 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF3	NM_031923.4 linkuse as main transcript	c.1096C>A	p.Pro366Thr	missense_variant	3/7	ENST00000344293.6	NP_114129.1	Q5VWG9
TAF3	XM_011519741.2 linkuse as main transcript	c.1093C>A	p.Pro365Thr	missense_variant	3/7		XP_011518043.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF3	ENST00000344293.6 linkuse as main transcript	c.1096C>A	p.Pro366Thr	missense_variant	3/7	1	NM_031923.4	ENSP00000340271.5		Q5VWG9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000112

AC:

AN:

248954

Hom.:

AF XY:

0.000170

AC XY:

AN XY:

135080

show subpopulations

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:

0.000882

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461872

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000742

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000151

ExAC

AF:

0.000157

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 06, 2023

The c.1096C>A (p.P366T) alteration is located in exon 3 (coding exon 3) of the TAF3 gene. This alteration results from a C to A substitution at nucleotide position 1096, causing the proline (P) at amino acid position 366 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.024

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.74

M_CAP

Benign

0.011

MetaRNN

Benign

0.039

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.0

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

REVEL

Benign

0.088

Sift

Benign

0.077

Sift4G

Benign

0.083

Polyphen

0.90

Vest4

0.24

MutPred

0.26

Gain of phosphorylation at P366 (P = 0.0534);

MVP

0.15

MPC

0.56

ClinPred

0.12

GERP RS

3.5

Varity_R

0.029

gMVP

0.23

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over