rs143246552

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_031276.3(TEX11):c.466A>G(p.Met156Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000307 in 1,207,138 control chromosomes in the GnomAD database, including 1 homozygotes. There are 111 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 0.00049 ( 0 hom., 13 hem., cov: 22)

Exomes 𝑓: 0.00029 ( 1 hom. 98 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:1B:2

Conservation

PhyloP100: -0.243

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=0.007108569).

BS2

High Hemizygotes in GnomAd4 at 13 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX11	NM_031276.3 link	c.466A>G	p.Met156Val	missense_variant	Exon 7 of 30	ENST00000374333.7	NP_112566.2	Q8IYF3-3
TEX11	NM_001003811.2 link	c.511A>G	p.Met171Val	missense_variant	Exon 8 of 31		NP_001003811.1	Q8IYF3-1
TEX11	XM_017029649.1 link	c.466A>G	p.Met156Val	missense_variant	Exon 7 of 31		XP_016885138.1
TEX11	XM_011530994.2 link	c.466A>G	p.Met156Val	missense_variant	Exon 7 of 31		XP_011529296.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX11	ENST00000374333.7 link	c.466A>G	p.Met156Val	missense_variant	Exon 7 of 30	1	NM_031276.3	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3 link	c.511A>G	p.Met171Val	missense_variant	Exon 6 of 29	5		ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6 link	c.511A>G	p.Met171Val	missense_variant	Exon 8 of 31	2		ENSP00000379226.2	Q8IYF3-1

Frequencies

GnomAD3 genomes

AF:

0.000495

AC:

AN:

111201

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

33385

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000967

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00113

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:

0.000440

AC:

AN:

179693

Hom.:

AF XY:

0.000327

AC XY:

AN XY:

64311

show subpopulations

Gnomad AFR exome

AF:

0.00169

Gnomad AMR exome

AF:

0.000331

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00336

Gnomad SAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.000287

AC:

315

AN:

1095879

Hom.:

Cov.:

AF XY:

0.000271

AC XY:

AN XY:

361335

show subpopulations

Gnomad4 AFR exome

AF:

0.00201

Gnomad4 AMR exome

AF:

0.000342

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00799

Gnomad4 SAS exome

AF:

0.0000186

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000174

GnomAD4 genome

AF:

0.000494

AC:

AN:

111259

Hom.:

Cov.:

AF XY:

0.000389

AC XY:

AN XY:

33453

show subpopulations

Gnomad4 AFR

AF:

0.00163

Gnomad4 AMR

AF:

0.0000966

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00113

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000718

ESP6500AA

AF:

0.00183

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000437

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1Benign:1

Mar 29, 2024

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.Met171Val variant in TEX11 is classified as likely benign because it has been identified in 0.73% (245/33686) of East Asian chromosomes including 82 hemizygotes and 1 homozygote by gnomAD (http://gnomad.broadinstitute.org, v.4.0.0). In addition, computational prediction tools predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4. -

May 04, 2022

Mendelics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spermatogenic failure, X-linked, 2

Pathogenic:1

May 28, 2015

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not provided

Benign:1

Feb 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.95

BayesDel_noAF

Benign

-1.1

CADD

Benign

0.0020

DANN

Benign

0.31

DEOGEN2

Benign

0.035

.;T;T

FATHMM_MKL

Benign

0.0092

LIST_S2

Benign

0.28

T;T;.

M_CAP

Benign

0.0021

MetaRNN

Benign

0.0071

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.83

.;N;N

PrimateAI

Benign

0.33

PROVEAN

Benign

0.010

N;N;N

REVEL

Benign

0.0080

Sift

Benign

0.57

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.025

MVP

0.043

MPC

0.31

ClinPred

0.0066

GERP RS

-5.8

Varity_R

0.046

gMVP

0.085

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