chrX-105219034-G-A

Position:

• chrX-105219034-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_031274.5(TEX13A):​c.1160C>T​(p.Ala387Val) 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. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32133663).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX13A	NM_031274.5	c.1160C>T	p.Ala387Val	missense_variant	3/3	ENST00000600991.6
IL1RAPL2	NM_017416.2	c.357-14784G>A		intron_variant		ENST00000372582.6
TEX13A	NM_001291277.2	c.1160C>T	p.Ala387Val	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX13A	ENST00000600991.6	c.1160C>T	p.Ala387Val	missense_variant	3/3	1	NM_031274.5	P1
TEX13A	ENST00000609007.3	c.1160C>T	p.Ala387Val	missense_variant	3/3	1		P1
IL1RAPL2	ENST00000372582.6	c.357-14784G>A		intron_variant		1	NM_017416.2	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.1160C>T (p.A387V) alteration is located in exon 3 (coding exon 2) of the TEX13A gene. This alteration results from a C to T substitution at nucleotide position 1160, causing the alanine (A) at amino acid position 387 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	Uncertain	0.54
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.066	T;T
FATHMM_MKL	Benign	0.76	D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Benign	0.46	T
Sift4G	Uncertain	0.013	D;D
Polyphen		1.0	D;D
Vest4		0.39
MutPred		0.27		Gain of loop (P = 0.0851);Gain of loop (P = 0.0851);
MVP		0.24
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.16
gMVP		0.036

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-104463716;