X-101269209-C-T

Position:

chrX-101269209-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001168474.2(TAF7L):c.1115G>A(p.Arg372His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00884 in 1,207,700 control chromosomes in the GnomAD database, including 41 homozygotes. There are 3,523 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0072 ( 3 hom., 242 hem., cov: 23)

Exomes 𝑓: 0.0090 ( 38 hom. 3281 hem. )

Consequence

TAF7L
NM_001168474.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:3

Conservation

PhyloP100: -0.483

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.002762109).

BP6

Variant X-101269209-C-T is Benign according to our data. Variant chrX-101269209-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1205846.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-101269209-C-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.009 (9864/1095521) while in subpopulation MID AF= 0.0518 (214/4128). AF 95% confidence interval is 0.0462. There are 38 homozygotes in gnomad4_exome. There are 3281 alleles in male gnomad4_exome subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF7L	NM_001168474.2 link	c.1115G>A	p.Arg372His	missense_variant	13/13	ENST00000356784.2	NP_001161946.1	Q5H9L4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAF7L	ENST00000356784.2 link	c.1115G>A	p.Arg372His	missense_variant	13/13	1	NM_001168474.2	ENSP00000349235.1	Q5H9L4-2
TAF7L	ENST00000372907.7 link	c.1373G>A	p.Arg458His	missense_variant	13/13	1		ENSP00000361998.3	Q5H9L4-1
TAF7L	ENST00000324762.10 link	c.893G>A	p.Arg298His	missense_variant	11/11	2		ENSP00000320283.6	Q5H9L4-3

Frequencies

GnomAD3 genomes

AF:

0.00719

AC:

806

AN:

112129

Hom.:

Cov.:

AF XY:

0.00700

AC XY:

240

AN XY:

34303

show subpopulations

Gnomad AFR

AF:

0.00285

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0134

Gnomad ASJ

AF:

0.0188

Gnomad EAS

AF:

0.00279

Gnomad SAS

AF:

0.0107

Gnomad FIN

AF:

0.000490

Gnomad MID

AF:

0.0628

Gnomad NFE

AF:

0.00853

Gnomad OTH

AF:

0.0106

GnomAD3 exomes

AF:

0.00641

AC:

1165

AN:

181837

Hom.:

AF XY:

0.00668

AC XY:

444

AN XY:

66455

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.00295

Gnomad ASJ exome

AF:

0.0153

Gnomad EAS exome

AF:

0.00160

Gnomad SAS exome

AF:

0.0110

Gnomad FIN exome

AF:

0.000437

Gnomad NFE exome

AF:

0.00790

Gnomad OTH exome

AF:

0.0107

GnomAD4 exome

AF:

0.00900

AC:

9864

AN:

1095521

Hom.:

Cov.:

AF XY:

0.00909

AC XY:

3281

AN XY:

361087

show subpopulations

Gnomad4 AFR exome

AF:

0.00330

Gnomad4 AMR exome

AF:

0.00379

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.00133

Gnomad4 SAS exome

AF:

0.0108

Gnomad4 FIN exome

AF:

0.000791

Gnomad4 NFE exome

AF:

0.00949

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00724

AC:

812

AN:

112179

Hom.:

Cov.:

AF XY:

0.00704

AC XY:

242

AN XY:

34363

show subpopulations

Gnomad4 AFR

AF:

0.00285

Gnomad4 AMR

AF:

0.0134

Gnomad4 ASJ

AF:

0.0188

Gnomad4 EAS

AF:

0.00280

Gnomad4 SAS

AF:

0.0119

Gnomad4 FIN

AF:

0.000490

Gnomad4 NFE

AF:

0.00853

Gnomad4 OTH

AF:

0.0125

Alfa

AF:

0.00935

Hom.:

468

Bravo

AF:

0.00800

TwinsUK

AF:

0.0116

AC:

ALSPAC

AF:

0.0111

AC:

ESP6500AA

AF:

0.00417

AC:

ESP6500EA

AF:

0.00847

AC:

ExAC

AF:

0.00679

AC:

824

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.019

DANN

Benign

0.71

DEOGEN2

Benign

0.026

T;.;.

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.56

T;T;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

0.41

N;N;N

REVEL

Benign

0.019

Sift

Benign

0.54

T;T;T

Sift4G

Benign

0.57

T;T;T

Polyphen

0.0

B;P;.

Vest4

0.017

MVP

0.082

MPC

0.33

ClinPred

0.00072

GERP RS

-8.7

Varity_R

0.016

gMVP

0.012

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