Variant X-70553405-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031276.3(TEX11):c.2300T>C(p.Met767Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000372 in 1,076,535 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 1 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2300T>C	p.Met767Thr	missense_variant	27/30	ENST00000374333.7	NP_112566.2	Q8IYF3-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX11	ENST00000374333.7 linkuse as main transcript	c.2300T>C	p.Met767Thr	missense_variant	27/30	1	NM_031276.3	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2345T>C	p.Met782Thr	missense_variant	26/29	5		ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2345T>C	p.Met782Thr	missense_variant	28/31	2		ENSP00000379226.2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1370T>C	p.Met457Thr	missense_variant	16/19	2		ENSP00000363440.2	Q8IYF3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000592

AC:

AN:

168898

Hom.:

AF XY:

0.0000181

AC XY:

AN XY:

55344

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000413

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000372

AC:

AN:

1076535

Hom.:

Cov.:

AF XY:

0.00000291

AC XY:

AN XY:

343483

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000594

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:

0.00000121

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 27, 2022

The c.2345T>C (p.M782T) alteration is located in exon 28 (coding exon 26) of the TEX11 gene. This alteration results from a T to C substitution at nucleotide position 2345, causing the methionine (M) at amino acid position 782 to be replaced by a threonine (T). 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

0.26

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.19

.;.;T;T

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.76

T;T;T;.

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Uncertain

2.1

.;.;M;M

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-3.1

D;D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Uncertain

0.015

D;D;D;D

Polyphen

0.87

P;.;P;P

Vest4

0.48

MutPred

0.61

.;.;Gain of glycosylation at M782 (P = 0.037);Gain of glycosylation at M782 (P = 0.037);

MVP

0.13

MPC

0.48

ClinPred

0.45

GERP RS

5.0

Varity_R

0.46

gMVP

0.56

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