X-105219025-A-G

Position:

• chrX-105219025-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_031274.5(TEX13A):​c.1169T>C​(p.Phe390Ser) 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 pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 21)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.19

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.807

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX13A	NM_031274.5	c.1169T>C	p.Phe390Ser	missense_variant	3/3	ENST00000600991.6	NP_112564.1
IL1RAPL2	NM_017416.2	c.357-14793A>G		intron_variant		ENST00000372582.6	NP_059112.1
TEX13A	NM_001291277.2	c.1169T>C	p.Phe390Ser	missense_variant	3/3		NP_001278206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX13A	ENST00000600991.6	c.1169T>C	p.Phe390Ser	missense_variant	3/3	1	NM_031274.5	ENSP00000471604	P1
TEX13A	ENST00000609007.3	c.1169T>C	p.Phe390Ser	missense_variant	3/3	1		ENSP00000477478	P1
IL1RAPL2	ENST00000372582.6	c.357-14793A>G		intron_variant		1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes Cov.: 21

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 21

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

May 18, 2023

The c.1169T>C (p.F390S) alteration is located in exon 3 (coding exon 2) of the TEX13A gene. This alteration results from a T to C substitution at nucleotide position 1169, causing the phenylalanine (F) at amino acid position 390 to be replaced by a serine (S). 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	Pathogenic	0.97
BayesDel_addAF	Uncertain	0.069	T
BayesDel_noAF	Benign	-0.14
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T;T
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.069	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.64	T
MutationAssessor	Pathogenic	3.7	H;H
MutationTaster	Benign	1.0	D;D;D;D;N
PrimateAI	Uncertain	0.58	T
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.67
MutPred		0.66		Gain of disorder (P = 0.0245);Gain of disorder (P = 0.0245);
MVP		0.16
ClinPred		0.92	D
GERP RS		2.2
Varity_R		0.096
gMVP		0.35

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-104463707;