Variant X-70609145-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031276.3(TEX11):c.1825G>A(p.Glu609Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000415 in 1,204,747 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

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

Exomes 𝑓: 9.2e-7 ( 0 hom. 0 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.742

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05335769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.1825G>A	p.Glu609Lys	missense_variant	22/30	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.1825G>A	p.Glu609Lys	missense_variant	22/30	1	NM_031276.3	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.1870G>A	p.Glu624Lys	missense_variant	21/29	5		ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.1870G>A	p.Glu624Lys	missense_variant	23/31	2		ENSP00000379226.2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.895G>A	p.Glu299Lys	missense_variant	11/19	2		ENSP00000363440.2	Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.0000357

AC:

AN:

112200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34350

show subpopulations

Gnomad AFR

AF:

0.000130

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:

0.0000114

AC:

AN:

175707

Hom.:

AF XY:

0.00

AC XY:

AN XY:

60831

show subpopulations

Gnomad AFR exome

AF:

0.000157

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

9.15e-7

AC:

AN:

1092547

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

358547

show subpopulations

Gnomad4 AFR exome

AF:

0.0000381

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000357

AC:

AN:

112200

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34350

show subpopulations

Gnomad4 AFR

AF:

0.000130

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

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

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

Nov 13, 2024

The c.1870G>A (p.E624K) alteration is located in exon 23 (coding exon 21) of the TEX11 gene. This alteration results from a G to A substitution at nucleotide position 1870, causing the glutamic acid (E) at amino acid position 624 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

0.075

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.82

CADD

Benign

8.5

DANN

Benign

0.72

DEOGEN2

Benign

0.063

.;.;T;T

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.64

T;T;T;.

M_CAP

Benign

0.0055

MetaRNN

Benign

0.053

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

.;.;M;M

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.40

T;T;T;T

Sift4G

Benign

0.66

T;T;T;T

Polyphen

0.0040

B;.;P;P

Vest4

0.097

MutPred

0.30

.;.;Gain of ubiquitination at E624 (P = 0.023);Gain of ubiquitination at E624 (P = 0.023);

MVP

0.093

MPC

0.61

ClinPred

0.016

GERP RS

1.5

Varity_R

0.059

gMVP

0.074

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