X-105219698-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_031274.5(TEX13A):c.496G>A(p.Gly166Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000058 in 1,207,455 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., 9 hem., cov: 22)
  • Exomes 𝑓: 0.000042 (0 hom. 15 hem.)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.43

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 Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013491809).
• BS2: High Hemizygotes in GnomAd at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX13A	NM_031274.5	c.496G>A	p.Gly166Arg	missense_variant	3/3	ENST00000600991.6
IL1RAPL2	NM_017416.2	c.357-14120C>T		intron_variant		ENST00000372582.6
TEX13A	NM_001291277.2	c.496G>A	p.Gly166Arg	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX13A	ENST00000600991.6	c.496G>A	p.Gly166Arg	missense_variant	3/3	1	NM_031274.5	P1
TEX13A	ENST00000609007.3	c.496G>A	p.Gly166Arg	missense_variant	3/3	1		P1
IL1RAPL2	ENST00000372582.6	c.357-14120C>T		intron_variant		1	NM_017416.2	P1

Frequencies

GnomAD3 genomes AF: 0.000215 AC: 24 AN: 111617 Hom.: 0 Cov.: 22 AF XY: 0.000266 AC XY: 9 AN XY: 33813

Gnomad AFR AF: 0.000782

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000101 AC: 18 AN: 177652 Hom.: 0 AF XY: 0.0000769 AC XY: 5 AN XY: 65006

Gnomad AFR exome AF: 0.00115

Gnomad AMR exome AF: 0.000146

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000420 AC: 46 AN: 1095792 Hom.: 0 Cov.: 33 AF XY: 0.0000414 AC XY: 15 AN XY: 362044

Gnomad4 AFR exome AF: 0.000909

Gnomad4 AMR exome AF: 0.000114

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: 0.0000190

Gnomad4 OTH exome AF: 0.0000434

GnomAD4 genome AF: 0.000215 AC: 24 AN: 111663 Hom.: 0 Cov.: 22 AF XY: 0.000266 AC XY: 9 AN XY: 33869

Gnomad4 AFR AF: 0.000780

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000285 Hom.: 1

Bravo AF: 0.000310

ESP6500AA AF: 0.000551 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000124 AC: 15

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 31, 2023

The c.496G>A (p.G166R) 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 496, causing the glycine (G) at amino acid position 166 to be replaced by an arginine (R). 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	0.12
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.0060
Dann	Benign	0.61
DEOGEN2	Benign	0.0088	T;T
FATHMM_MKL	Benign	0.00033	N
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.013	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.31	T
Sift4G	Benign	0.22	T;T
Polyphen		0.0020	B;B
Vest4		0.063
MutPred		0.15		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);
MVP		0.030
ClinPred		0.0015	T
GERP RS		-3.0
Varity_R		0.066
gMVP		0.028

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs370620805; hg19: chrX-104464382; COSMIC: COSV61162455;