Variant X-101282381-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001168474.2(TAF7L):c.352A>G(p.Ile118Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000405 in 1,208,935 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000037 ( 0 hom. 15 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.409

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035093874).

BP6

Variant X-101282381-T-C is Benign according to our data. Variant chrX-101282381-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3324287.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2 link	c.352A>G	p.Ile118Val	missense_variant	5/13	ENST00000356784.2	NP_001161946.1	Q5H9L4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAF7L	ENST00000356784.2 link	c.352A>G	p.Ile118Val	missense_variant	5/13	1	NM_001168474.2	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7 link	c.610A>G	p.Ile204Val	missense_variant	5/13	1		ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10 link	c.352A>G	p.Ile118Val	missense_variant	4/11	2		ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.0000717

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33675

show subpopulations

Gnomad AFR

AF:

0.0000326

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000436

AC:

AN:

183467

Hom.:

AF XY:

0.0000442

AC XY:

AN XY:

67907

show subpopulations

Gnomad AFR exome

AF:

0.000152

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:

0.0000732

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1097428

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

362784

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000452

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000717

AC:

AN:

111507

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

33675

show subpopulations

Gnomad4 AFR

AF:

0.0000326

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.062

DANN

Benign

0.28

DEOGEN2

Benign

0.018

T;.;.

FATHMM_MKL

Benign

0.0075

LIST_S2

Benign

0.28

T;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.035

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.70

N;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.58

N;N;N

REVEL

Benign

0.019

Sift

Benign

1.0

T;T;T

Sift4G

Benign

0.68

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.058

MVP

0.043

MPC

0.22

ClinPred

0.013

GERP RS

-0.48

Varity_R

0.032

gMVP

0.069

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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