Variant X-101278103-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PP3_ModerateBS2

The NM_001168474.2(TAF7L):c.523G>A(p.Val175Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000108 in 1,208,678 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.0000091 ( 0 hom. 6 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.37

Variant links:

Genes affected

TAF7L (HGNC:11548): (TATA-box binding protein associated factor 7 like) This gene is similar to a mouse gene that encodes a TATA box binding protein-associated factor, and shows testis-specific expression. The encoded protein could be a spermatogenesis-specific component of the DNA-binding general transcription factor complex TFIID. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2009]

TAF7L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.913

BS2

High Hemizygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2 linkuse as main transcript	c.523G>A	p.Val175Met	missense_variant	8/13	ENST00000356784.2	NP_001161946.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF7L	ENST00000356784.2 linkuse as main transcript	c.523G>A	p.Val175Met	missense_variant	8/13	1	NM_001168474.2	ENSP00000349235	A2	Q5H9L4-2
TAF7L	ENST00000372907.7 linkuse as main transcript	c.781G>A	p.Val261Met	missense_variant	8/13	1		ENSP00000361998	P2	Q5H9L4-1
TAF7L	ENST00000324762.10 linkuse as main transcript	c.523G>A	p.Val175Met	missense_variant	7/11	2		ENSP00000320283	A2	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.0000268

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33955

show subpopulations

Gnomad AFR

AF:

0.0000325

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000950

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000280

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000109

AC:

AN:

183097

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67585

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000122

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000912

AC:

AN:

1096897

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

362273

show subpopulations

Gnomad4 AFR exome

AF:

0.0000758

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000662

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000595

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000268

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33955

show subpopulations

Gnomad4 AFR

AF:

0.0000325

Gnomad4 AMR

AF:

0.0000950

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000280

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

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

Feb 10, 2023

The c.781G>A (p.V261M) alteration is located in exon 8 (coding exon 8) of the TAF7L gene. This alteration results from a G to A substitution at nucleotide position 781, causing the valine (V) at amino acid position 261 to be replaced by a methionine (M). 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

0.21

BayesDel_addAF

Uncertain

0.062

BayesDel_noAF

Uncertain

0.040

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Pathogenic

0.58

MetaRNN

Pathogenic

0.91

D;D;D

MetaSVM

Benign

-0.48

MutationAssessor

Pathogenic

3.6

H;.;.

MutationTaster

Benign

0.99

D;D;D;D

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Uncertain

0.36

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;.

Vest4

0.78

MutPred

0.73

Gain of ubiquitination at K266 (P = 0.0575);.;.;

MVP

0.83

MPC

0.94

ClinPred

0.75

GERP RS

4.2

Varity_R

0.39

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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