Variant X-70554747-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_031276.3(TEX11):c.2194G>A(p.Val732Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000712 in 1,208,406 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 26 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., 12 hem., cov: 23)

Exomes 𝑓: 0.000041 ( 0 hom. 14 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.54

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=0.03871435).

BP6

Variant X-70554747-C-T is Benign according to our data. Variant chrX-70554747-C-T is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAd4 at 12 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2194G>A	p.Val732Ile	missense_variant	26/30	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.2194G>A	p.Val732Ile	missense_variant	26/30	1	NM_031276.3	ENSP00000363453.2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2239G>A	p.Val747Ile	missense_variant	25/29	5		ENSP00000340995.3	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2239G>A	p.Val747Ile	missense_variant	27/31	2		ENSP00000379226.2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1264G>A	p.Val422Ile	missense_variant	15/19	2		ENSP00000363440.2	Q8IYF3-2

Frequencies

GnomAD3 genomes

AF:

0.000367

AC:

AN:

111833

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

34009

show subpopulations

Gnomad AFR

AF:

0.00120

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000191

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:

0.0000377

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

180556

Hom.:

AF XY:

0.0000613

AC XY:

AN XY:

65236

show subpopulations

Gnomad AFR exome

AF:

0.000846

Gnomad AMR exome

AF:

0.000261

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:

0.0000247

Gnomad OTH exome

AF:

0.000225

GnomAD4 exome

AF:

0.0000410

AC:

AN:

1096573

Hom.:

Cov.:

AF XY:

0.0000387

AC XY:

AN XY:

362151

show subpopulations

Gnomad4 AFR exome

AF:

0.000950

Gnomad4 AMR exome

AF:

0.000228

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:

0.00000475

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000367

AC:

AN:

111833

Hom.:

Cov.:

AF XY:

0.000353

AC XY:

AN XY:

34009

show subpopulations

Gnomad4 AFR

AF:

0.00120

Gnomad4 AMR

AF:

0.000191

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000377

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.000412

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.000124

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

Sep 30, 2024

The c.2239G>A (p.V747I) alteration is located in exon 27 (coding exon 25) of the TEX11 gene. This alteration results from a G to A substitution at nucleotide position 2239, causing the valine (V) at amino acid position 747 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.060

.;.;T;T

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.75

T;T;T;.

M_CAP

Benign

0.0063

MetaRNN

Benign

0.039

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;.;L;L

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.58

N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.071

T;T;T;T

Sift4G

Benign

0.22

T;T;T;T

Polyphen

0.30

B;.;B;B

Vest4

0.10

MVP

0.19

MPC

0.28

ClinPred

0.018

GERP RS

3.5

Varity_R

0.11

gMVP

0.14

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