X-70610514-C-T

Position:

chrX-70610514-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_031276.3(TEX11):c.1781G>A(p.Cys594Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000531 in 1,205,491 control chromosomes in the GnomAD database, including 1 homozygotes. There are 20 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 3 hem., cov: 22)

Exomes 𝑓: 0.000050 ( 1 hom. 17 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 0.0800

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014674038).

BP6

Variant X-70610514-C-T is Benign according to our data. Variant chrX-70610514-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2660830.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High Hemizygotes in GnomAd4 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.1781G>A	p.Cys594Tyr	missense_variant	21/30	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.1781G>A	p.Cys594Tyr	missense_variant	21/30	1	NM_031276.3	ENSP00000363453	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.1826G>A	p.Cys609Tyr	missense_variant	20/29	5		ENSP00000340995	A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.1826G>A	p.Cys609Tyr	missense_variant	22/31	2		ENSP00000379226	A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.851G>A	p.Cys284Tyr	missense_variant	10/19	2		ENSP00000363440		Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.0000810

AC:

AN:

111151

Hom.:

Cov.:

AF XY:

0.0000898

AC XY:

AN XY:

33391

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000958

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00225

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:

0.000223

AC:

AN:

179215

Hom.:

AF XY:

0.000188

AC XY:

AN XY:

63927

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00295

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000503

AC:

AN:

1094292

Hom.:

Cov.:

AF XY:

0.0000472

AC XY:

AN XY:

359946

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00183

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000809

AC:

AN:

111199

Hom.:

Cov.:

AF XY:

0.0000897

AC XY:

AN XY:

33449

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000957

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00226

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000106

ExAC

AF:

0.000165

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.1826G>A (p.C609Y) alteration is located in exon 22 (coding exon 20) of the TEX11 gene. This alteration results from a G to A substitution at nucleotide position 1826, causing the cysteine (C) at amino acid position 609 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

TEX11: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.1

DANN

Benign

0.20

DEOGEN2

Benign

0.039

.;.;T;T

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.63

T;T;T;.

M_CAP

Benign

0.011

MetaRNN

Benign

0.015

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

.;.;N;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

0.58

N;N;N;N

REVEL

Benign

0.040

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.79

T;T;T;T

Polyphen

0.0

B;.;B;B

Vest4

0.17

MutPred

0.43

.;.;Loss of catalytic residue at L610 (P = 0.0473);Loss of catalytic residue at L610 (P = 0.0473);

MVP

0.068

MPC

0.52

ClinPred

0.0078

GERP RS

0.76

Varity_R

0.064

gMVP

0.32

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