Variant X-70553329-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031276.3(TEX11):c.2376A>T(p.Glu792Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 112,367 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.538

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06460908).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2376A>T	p.Glu792Asp	missense_variant	27/30	ENST00000374333.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX11	ENST00000374333.7 linkuse as main transcript	c.2376A>T	p.Glu792Asp	missense_variant	27/30	1	NM_031276.3	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2421A>T	p.Glu807Asp	missense_variant	26/29	5		A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2421A>T	p.Glu807Asp	missense_variant	28/31	2		A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1446A>T	p.Glu482Asp	missense_variant	16/19	2			Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.00000890

AC:

AN:

112367

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34511

show subpopulations

Gnomad AFR

AF:

0.0000323

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000890

AC:

AN:

112367

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34511

show subpopulations

Gnomad4 AFR

AF:

0.0000323

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

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

Aug 15, 2023

The c.2421A>T (p.E807D) alteration is located in exon 28 (coding exon 26) of the TEX11 gene. This alteration results from a A to T substitution at nucleotide position 2421, causing the glutamic acid (E) at amino acid position 807 to be replaced by an aspartic acid (D). 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

0.085

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.99

CADD

Benign

0.17

DANN

Benign

0.75

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.37

T;T;T;.

M_CAP

Benign

0.0044

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.96

N;N;N;N

REVEL

Benign

0.0040

Sift

Benign

0.43

T;T;T;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.099

B;.;B;B

Vest4

0.058

MutPred

0.30

.;.;Loss of ubiquitination at K805 (P = 0.0954);Loss of ubiquitination at K805 (P = 0.0954);

MVP

0.093

MPC

0.29

ClinPred

0.049

GERP RS

-2.4

Varity_R

0.059

gMVP

0.13

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