Variant X-124333893-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001355534.2(TEX13D):c.976G>A(p.Gly326Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000822 in 353,907 control chromosomes in the GnomAD database, including 2 homozygotes. There are 87 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 7/10 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00081 ( 0 hom., 25 hem., cov: 21)

Exomes 𝑓: 0.00083 ( 2 hom. 62 hem. )

Consequence

TEX13D
NM_001355534.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.260

Variant links:

Genes affected

TEX13D (HGNC:52278): (TEX13 family member D) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

TEX13D links:

STAG2 (HGNC:11355): (STAG2 cohesin complex component) The protein encoded by this gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

STAG2 links:

SH2D1A (HGNC:10820): (SH2 domain containing 1A) This gene encodes a protein that plays a major role in the bidirectional stimulation of T and B cells. This protein contains an SH2 domain and a short tail. It associates with the signaling lymphocyte-activation molecule, thereby acting as an inhibitor of this transmembrane protein by blocking the recruitment of the SH2-domain-containing signal-transduction molecule SHP-2 to its docking site. This protein can also bind to other related surface molecules that are expressed on activated T, B and NK cells, thereby modifying signal transduction pathways in these cells. Mutations in this gene cause lymphoproliferative syndrome X-linked type 1 or Duncan disease, a rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus, with symptoms including severe mononucleosis and malignant lymphoma. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

SH2D1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010283977).

BP6

Variant X-124333893-G-A is Benign according to our data. Variant chrX-124333893-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661356.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 25 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX13D	NM_001355534.2 linkuse as main transcript	c.976G>A	p.Gly326Arg	missense_variant	1/1	ENST00000632372.3	NP_001342463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX13D	ENST00000632372.3 linkuse as main transcript	c.976G>A	p.Gly326Arg	missense_variant	1/1		NM_001355534.2	ENSP00000488696	P1

Frequencies

GnomAD3 genomes

AF:

0.000810

AC:

AN:

109880

Hom.:

Cov.:

AF XY:

0.000776

AC XY:

AN XY:

32220

show subpopulations

Gnomad AFR

AF:

0.000166

Gnomad AMI

AF:

0.0152

Gnomad AMR

AF:

0.00104

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:

0.00120

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000828

AC:

202

AN:

243978

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

69984

show subpopulations

Gnomad4 AFR exome

AF:

0.000449

Gnomad4 AMR exome

AF:

0.00105

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000913

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00101

Gnomad4 OTH exome

AF:

0.000890

GnomAD4 genome

AF:

0.000810

AC:

AN:

109929

Hom.:

Cov.:

AF XY:

0.000774

AC XY:

AN XY:

32279

show subpopulations

Gnomad4 AFR

AF:

0.000166

Gnomad4 AMR

AF:

0.00104

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00120

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000854

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000692

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2022

TEX13D: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.5

DANN

Benign

0.37

FATHMM_MKL

Benign

0.0050

LIST_S2

Benign

0.32

MetaRNN

Benign

0.010

Sift4G

Benign

0.16

Vest4

0.10

GERP RS

1.4

Varity_R

0.057

gMVP

0.025

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