X-124335002-G-A

Variant names:

• chrX-124335002-G-A
• rs745604663
• NM_001355534.2:c.2085G>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001355534.2(TEX13D):​c.2085G>A​(p.Thr695Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000861 in 937,274 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 256 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00059 (0 hom., 24 hem., cov: 24)
  • Exomes 𝑓: 0.00090 (0 hom. 232 hem.)
• Consequence: TEX13D NM_001355534.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.689
• 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant X-124335002-G-A is Benign according to our data. Variant chrX-124335002-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2661358.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.689 with no splicing effect.
• BS2: High Hemizygotes in GnomAd4 at 24 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.2085G>A	p.Thr695Thr	synonymous	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.2085G>A	p.Thr695Thr	synonymous	Exon 1 of 1	ENSP00000488696.1	A0A0J9YY54
	STAG2	ENST00000469481.1	TSL:3	n.454-76820G>A		intron	N/A
	TEX13D	ENST00000635518.1	TSL:5	n.90-350G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000595 AC: 67 AN: 112598 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000226

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: 0.00227

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000863

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000897 AC: 740 AN: 824623 Hom.: 0 Cov.: 30 AF XY: 0.000911 AC XY: 232 AN XY: 254715

African (AFR) AF: 0.000166 AC: 3 AN: 18026

American (AMR) AF: 0.00 AC: 0 AN: 6460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10666

East Asian (EAS) AF: 0.00 AC: 0 AN: 20451

South Asian (SAS) AF: 0.00 AC: 0 AN: 14173

European-Finnish (FIN) AF: 0.00327 AC: 53 AN: 16205

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2022

European-Non Finnish (NFE) AF: 0.000942 AC: 662 AN: 702872

Other (OTH) AF: 0.000652 AC: 22 AN: 33748

GnomAD4 genome AF: 0.000595 AC: 67 AN: 112651 Hom.: 0 Cov.: 24 AF XY: 0.000689 AC XY: 24 AN XY: 34821

African (AFR) AF: 0.000226 AC: 7 AN: 31021

American (AMR) AF: 0.00 AC: 0 AN: 10771

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3568

South Asian (SAS) AF: 0.00 AC: 0 AN: 2726

European-Finnish (FIN) AF: 0.00227 AC: 14 AN: 6161

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 218

European-Non Finnish (NFE) AF: 0.000863 AC: 46 AN: 53302

Other (OTH) AF: 0.00 AC: 0 AN: 1541

Alfa AF: 0.000648 Hom.: 2

Bravo AF: 0.000457

ClinVar

ClinVar submissions

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
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.11
DANN	Benign	0.61
PhyloP100		-0.69

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: rs745604663; hg19: chrX-123468852;