Variant X-70554699-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_031276.3(TEX11):c.2242G>T(p.Val748Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000406 in 1,207,625 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 8 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V748A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.000037 ( 0 hom. 8 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.310

Variant links:

Genes affected

TEX11 (HGNC:11733): (testis expressed 11) This gene is X-linked and is expressed in only male germ cells. Two alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

TEX11 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=0.025094956).

BS2

High Hemizygotes in GnomAdExome4 at 8 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2242G>T	p.Val748Leu	missense_variant	26/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7 linkuse as main transcript	c.2242G>T	p.Val748Leu	missense_variant	26/30	1	NM_031276.3	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2287G>T	p.Val763Leu	missense_variant	25/29	5		A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2287G>T	p.Val763Leu	missense_variant	27/31	2		A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1312G>T	p.Val438Leu	missense_variant	15/19	2			Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.0000715

AC:

AN:

111869

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34039

show subpopulations

Gnomad AFR

AF:

0.0000324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00140

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000376

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000838

AC:

AN:

178950

Hom.:

AF XY:

0.0000471

AC XY:

AN XY:

63698

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000965

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000249

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000374

AC:

AN:

1095756

Hom.:

Cov.:

AF XY:

0.0000221

AC XY:

AN XY:

361408

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000599

Gnomad4 SAS exome

AF:

0.0000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000262

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000715

AC:

AN:

111869

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34039

show subpopulations

Gnomad4 AFR

AF:

0.0000324

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00140

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000376

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2023

The c.2287G>T (p.V763L) alteration is located in exon 27 (coding exon 25) of the TEX11 gene. This alteration results from a G to T substitution at nucleotide position 2287, causing the valine (V) at amino acid position 763 to be replaced by a leucine (L). 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

0.17

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Uncertain

0.99

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.60

T;T;T;.

M_CAP

Benign

0.017

MetaRNN

Benign

0.025

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.94

N;N;N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.042

Sift

Benign

0.11

T;T;T;T

Sift4G

Uncertain

0.027

D;D;D;D

Polyphen

0.0080

B;.;B;B

Vest4

0.14

MutPred

0.61

.;.;Gain of phosphorylation at S758 (P = 0.2085);Gain of phosphorylation at S758 (P = 0.2085);

MVP

0.23

MPC

0.33

ClinPred

0.071

GERP RS

2.5

Varity_R

0.19

gMVP

0.40

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