chrX-105219260-A-G

Position:

• chrX-105219260-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The ENST00000600991.6(TEX13A):​c.934T>C​(p.Ser312Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TEX13A ENST00000600991.6 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0630

Genes affected

TEX13A (HGNC:11735): (testis expressed 13A) This gene is similar to a mouse gene that is expressed in the testis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

IL1RAPL2 (HGNC:5997): (interleukin 1 receptor accessory protein like 2) The protein encoded by this gene is a member of the interleukin 1 receptor family. This protein is similar to the interleukin 1 accessory proteins, and is most closely related to interleukin 1 receptor accessory protein-like 1 (IL1RAPL1). This gene and IL1RAPL1 are located at a region on chromosome X that is associated with X-linked non-syndromic cognitive disability. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.052756608).
• BP6: Variant X-105219260-A-G is Benign according to our data. Variant chrX-105219260-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3176272.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX13A	NM_031274.5	c.934T>C	p.Ser312Pro	missense_variant	3/3	ENST00000600991.6	NP_112564.1
IL1RAPL2	NM_017416.2	c.357-14558A>G		intron_variant		ENST00000372582.6	NP_059112.1
TEX13A	NM_001291277.2	c.934T>C	p.Ser312Pro	missense_variant	3/3		NP_001278206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX13A	ENST00000600991.6	c.934T>C	p.Ser312Pro	missense_variant	3/3	1	NM_031274.5	ENSP00000471604	P1
TEX13A	ENST00000609007.3	c.934T>C	p.Ser312Pro	missense_variant	3/3	1		ENSP00000477478	P1
IL1RAPL2	ENST00000372582.6	c.357-14558A>G		intron_variant		1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 20, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.1
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0034	T;T
FATHMM_MKL	Benign	0.00046	N
LIST_S2	Benign	0.29	.;T
M_CAP	Benign	0.0038	T
MetaRNN	Benign	0.053	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.36	N;N
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.34	T
Sift4G	Benign	0.49	T;T
Polyphen		0.0	B;B
Vest4		0.030
MutPred		0.14		Loss of glycosylation at S312 (P = 0.021);Loss of glycosylation at S312 (P = 0.021);
MVP		0.040
ClinPred		0.18	T
GERP RS		1.3
Varity_R		0.090
gMVP		0.024

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.

Other links and lift over

hg19: chrX-104463942;