rs775432134

Variant names:

• chrX-124333893-G-A
• rs775432134
• NM_001355534.2:c.976G>A

Your query was ambiguous. Multiple possible variants found:

• chrX-124333893-G-A
• chrX-124333893-G-C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.260
• Publications: 0 publications found

Genes affected

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

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]

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 Gene-Disease associations (from GenCC):

• X-linked lymphoproliferative disease due to SH2D1A deficiency

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen, G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 2661356.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd4 at 25 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001355534.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13D	NM_001355534.2	MANE Select	c.976G>A	p.Gly326Arg	missense	Exon 1 of 1	NP_001342463.1	A0A0J9YY54

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13D	ENST00000632372.3	TSL:6 MANE Select	c.976G>A	p.Gly326Arg	missense	Exon 1 of 1	ENSP00000488696.1	A0A0J9YY54
	STAG2	ENST00000469481.1	TSL:3	n.454-77929G>A		intron	N/A
	TEX13D	ENST00000635518.1	TSL:5	n.90-1459G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000810 AC: 89 AN: 109880 Hom.: 0 Cov.: 21

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.: 2 Cov.: 5 AF XY: 0.000886 AC XY: 62 AN XY: 69984

African (AFR) AF: 0.000449 AC: 3 AN: 6680

American (AMR) AF: 0.00105 AC: 6 AN: 5725

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7077

East Asian (EAS) AF: 0.00 AC: 0 AN: 17768

South Asian (SAS) AF: 0.000913 AC: 3 AN: 3287

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15975

Middle Eastern (MID) AF: 0.00303 AC: 3 AN: 991

European-Non Finnish (NFE) AF: 0.00101 AC: 174 AN: 171862

Other (OTH) AF: 0.000890 AC: 13 AN: 14613

GnomAD4 genome AF: 0.000810 AC: 89 AN: 109929 Hom.: 0 Cov.: 21 AF XY: 0.000774 AC XY: 25 AN XY: 32279

African (AFR) AF: 0.000166 AC: 5 AN: 30138

American (AMR) AF: 0.00104 AC: 11 AN: 10543

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2623

East Asian (EAS) AF: 0.00 AC: 0 AN: 3428

South Asian (SAS) AF: 0.00 AC: 0 AN: 2497

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5947

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 207

European-Non Finnish (NFE) AF: 0.00120 AC: 63 AN: 52393

Other (OTH) AF: 0.00 AC: 0 AN: 1496

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000854

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000692 AC: 2

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

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	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.010	T
PhyloP100		-0.26
Sift4G	Benign	0.16	T
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

Other links and lift over

dbSNP: rs775432134; hg19: chrX-123467743;