Variant X-70529906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_031276.3(TEX11):c.2614G>A(p.Glu872Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,209,578 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 30 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 (★).

Frequency

Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000077 ( 0 hom. 29 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.18

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.20627528).

BS2

High Hemizygotes in GnomAdExome4 at 29 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2614G>A	p.Glu872Lys	missense_variant	29/30	ENST00000374333.7	NP_112566.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX11	ENST00000374333.7 linkuse as main transcript	c.2614G>A	p.Glu872Lys	missense_variant	29/30	1	NM_031276.3	ENSP00000363453	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2659G>A	p.Glu887Lys	missense_variant	28/29	5		ENSP00000340995	A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2659G>A	p.Glu887Lys	missense_variant	30/31	2		ENSP00000379226	A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1684G>A	p.Glu562Lys	missense_variant	18/19	2		ENSP00000363440		Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.0000358

AC:

AN:

111735

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33911

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000752

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000710

AC:

AN:

183222

Hom.:

AF XY:

0.0000886

AC XY:

AN XY:

67686

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000159

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000774

AC:

AN:

1097843

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

363207

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000986

Gnomad4 OTH exome

AF:

0.0000434

GnomAD4 genome

AF:

0.0000358

AC:

AN:

111735

Hom.:

Cov.:

AF XY:

0.0000295

AC XY:

AN XY:

33911

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000752

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

Jan 03, 2024

The c.2659G>A (p.E887K) alteration is located in exon 30 (coding exon 28) of the TEX11 gene. This alteration results from a G to A substitution at nucleotide position 2659, causing the glutamic acid (E) at amino acid position 887 to be replaced by a lysine (K). 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

0.18

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.095

.;.;T;T

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.85

T;T;T;.

M_CAP

Benign

0.018

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.71

MutationAssessor

Uncertain

2.0

.;.;M;M

MutationTaster

Benign

0.72

D;D;D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.14

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.87

P;.;P;P

Vest4

0.33

MVP

0.15

MPC

0.38

ClinPred

0.31

GERP RS

3.5

Varity_R

0.35

gMVP

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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