Variant X-70553406-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031276.3(TEX11):c.2299A>G(p.Met767Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000934 in 1,070,396 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 9.3e-7 ( 0 hom. 0 hem. )

Consequence

TEX11
NM_031276.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21173006).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX11	NM_031276.3 linkuse as main transcript	c.2299A>G	p.Met767Val	missense_variant	27/30	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.2299A>G	p.Met767Val	missense_variant	27/30	1	NM_031276.3	ENSP00000363453	P2	Q8IYF3-3
TEX11	ENST00000344304.3 linkuse as main transcript	c.2344A>G	p.Met782Val	missense_variant	26/29	5		ENSP00000340995	A2	Q8IYF3-1
TEX11	ENST00000395889.6 linkuse as main transcript	c.2344A>G	p.Met782Val	missense_variant	28/31	2		ENSP00000379226	A2	Q8IYF3-1
TEX11	ENST00000374320.6 linkuse as main transcript	c.1369A>G	p.Met457Val	missense_variant	16/19	2		ENSP00000363440		Q8IYF3-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.34e-7

AC:

AN:

1070396

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

338032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

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

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

Jul 09, 2021

The c.2344A>G (p.M782V) alteration is located in exon 28 (coding exon 26) of the TEX11 gene. This alteration results from a A to G substitution at nucleotide position 2344, causing the methionine (M) at amino acid position 782 to be replaced by a valine (V). 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

0.084

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.73

CADD

Benign

3.3

DANN

Benign

0.77

DEOGEN2

Benign

0.18

.;.;T;T

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.71

T;T;T;.

M_CAP

Benign

0.0039

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

.;.;L;L

MutationTaster

Benign

0.98

N;N;N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.3

N;D;N;N

REVEL

Benign

0.074

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.081

T;T;T;T

Polyphen

0.021

B;.;B;B

Vest4

0.16

MutPred

0.71

.;.;Gain of ubiquitination at K784 (P = 0.0954);Gain of ubiquitination at K784 (P = 0.0954);

MVP

0.082

MPC

0.31

ClinPred

0.14

GERP RS

1.1

Varity_R

0.13

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over