Variant X-70529120-T-C 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.2753A>G(p.His918Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000827 in 1,208,689 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000082 ( 0 hom. 3 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.789

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=0.107063234).

BS2

High Hemizygotes in GnomAdExome4 at 3 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2753A>G	p.His918Arg	missense_variant	30/30	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.2753A>G	p.His918Arg	missense_variant	30/30	1	NM_031276.3	ENSP00000363453	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2798A>G	p.His933Arg	missense_variant	29/29	5		ENSP00000340995	A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2798A>G	p.His933Arg	missense_variant	31/31	2		ENSP00000379226	A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1823A>G	p.His608Arg	missense_variant	19/19	2		ENSP00000363440		Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33953

show subpopulations

Gnomad AFR

AF:

0.0000325

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

GnomAD3 exomes

AF:

0.0000218

AC:

AN:

183112

Hom.:

AF XY:

0.00

AC XY:

AN XY:

67608

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000730

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:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000820

AC:

AN:

1096908

Hom.:

Cov.:

AF XY:

0.00000828

AC XY:

AN XY:

362300

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000114

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:

0.00000476

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000895

AC:

AN:

111781

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33953

show subpopulations

Gnomad4 AFR

AF:

0.0000325

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:

0.0000302

ExAC

AF:

0.00000824

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

Dec 27, 2022

The c.2798A>G (p.H933R) alteration is located in exon 31 (coding exon 29) of the TEX11 gene. This alteration results from a A to G substitution at nucleotide position 2798, causing the histidine (H) at amino acid position 933 to be replaced by an arginine (R). 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

0.067

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.6

DANN

Benign

0.85

DEOGEN2

Benign

0.033

.;.;T;T

FATHMM_MKL

Benign

0.069

LIST_S2

Benign

0.48

T;T;T;.

M_CAP

Benign

0.0040

MetaRNN

Benign

0.11

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.29

N;N;N;N

REVEL

Benign

0.013

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

0.088

T;T;T;T

Polyphen

0.027

B;.;B;B

Vest4

0.23

MutPred

0.24

.;.;Gain of MoRF binding (P = 0.025);Gain of MoRF binding (P = 0.025);

MVP

0.068

MPC

0.37

ClinPred

0.11

GERP RS

3.3

Varity_R

0.078

gMVP

0.061

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