X-105219331-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031274.5(TEX13A):c.863C>T(p.Ser288Leu) 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. 12/16 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: 2.13

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.078433186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX13A	NM_031274.5	c.863C>T	p.Ser288Leu	missense_variant	3/3	ENST00000600991.6
IL1RAPL2	NM_017416.2	c.357-14487G>A		intron_variant		ENST00000372582.6
TEX13A	NM_001291277.2	c.863C>T	p.Ser288Leu	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX13A	ENST00000600991.6	c.863C>T	p.Ser288Leu	missense_variant	3/3	1	NM_031274.5	P1
TEX13A	ENST00000609007.3	c.863C>T	p.Ser288Leu	missense_variant	3/3	1		P1
IL1RAPL2	ENST00000372582.6	c.357-14487G>A		intron_variant		1	NM_017416.2	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 33

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

Dec 22, 2023

The c.863C>T (p.S288L) 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 863, causing the serine (S) at amino acid position 288 to be replaced by a leucine (L). 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	Benign	0.13
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
Cadd	Benign	16
Dann	Benign	0.90
DEOGEN2	Benign	0.016	T;T
FATHMM_MKL	Benign	0.075	N
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.078	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.28	T
Sift4G	Benign	0.13	T;T
Polyphen		0.020	B;B
Vest4		0.13
MutPred		0.21		Loss of phosphorylation at S288 (P = 0.0157);Loss of phosphorylation at S288 (P = 0.0157);
MVP		0.030
ClinPred		0.048	T
GERP RS		2.6
Varity_R		0.052
gMVP		0.043

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-104464013;