X-105219677-C-T

Variant names:

• chrX-105219677-C-T
• NM_031274.5:c.517G>A

Variant summary

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

The NM_031274.5(TEX13A):​c.517G>A​(p.Ala173Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,096,801 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/15 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)
  • Exomes 𝑓: 0.0000036 (0 hom. 1 hem.)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.491

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05242309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX13A	NM_031274.5	c.517G>A	p.Ala173Thr	missense_variant	Exon 3 of 3	ENST00000600991.6	NP_112564.1
IL1RAPL2	NM_017416.2	c.357-14141C>T		intron_variant	Intron 3 of 10	ENST00000372582.6	NP_059112.1
TEX13A	NM_001291277.2	c.517G>A	p.Ala173Thr	missense_variant	Exon 3 of 3		NP_001278206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX13A	ENST00000600991.6	c.517G>A	p.Ala173Thr	missense_variant	Exon 3 of 3	1	NM_031274.5	ENSP00000471604.2
TEX13A	ENST00000609007.3	c.517G>A	p.Ala173Thr	missense_variant	Exon 3 of 3	1		ENSP00000477478.2
IL1RAPL2	ENST00000372582.6	c.357-14141C>T		intron_variant	Intron 3 of 10	1	NM_017416.2	ENSP00000361663.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000365 AC: 4 AN: 1096801 Hom.: 0 Cov.: 33 AF XY: 0.00000276 AC XY: 1 AN XY: 362681

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000475

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 29, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.517G>A (p.A173T) alteration is located in exon 3 (coding exon 2) of the TEX13A gene. This alteration results from a G to A substitution at nucleotide position 517, causing the alanine (A) at amino acid position 173 to be replaced by a threonine (T). 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	0.10
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-1.0
CADD	Benign	6.3
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T
FATHMM_MKL	Benign	0.0093	N
LIST_S2	Benign	0.38	.;T
M_CAP	Benign	0.0081	T
MetaRNN	Benign	0.052	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.30	T
Sift4G	Benign	0.10	T;T
Polyphen		0.030	B;B
Vest4		0.046
MutPred		0.15		Gain of glycosylation at A173 (P = 0.005);Gain of glycosylation at A173 (P = 0.005);
MVP		0.048
ClinPred		0.19	T
GERP RS		-3.5
Varity_R		0.031
gMVP		0.044

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-104464361;