chrX-105219970-C-T

Variant names:

• chrX-105219970-C-T
• rs782792744
• NM_031274.5:c.428G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_031274.5(TEX13A):​c.428G>A​(p.Arg143Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000368 in 1,085,689 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. 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: 23)
  • Exomes 𝑓: 0.0000037 (0 hom. 1 hem.)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.933
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06557834).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031274.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13A	NM_031274.5	MANE Select	c.428G>A	p.Arg143Lys	missense	Exon 2 of 3	NP_112564.1	Q9BXU3
	IL1RAPL2	NM_017416.2	MANE Select	c.357-13848C>T		intron	N/A	NP_059112.1	Q9NP60
	TEX13A	NM_001291277.2		c.428G>A	p.Arg143Lys	missense	Exon 2 of 3	NP_001278206.1	Q9BXU3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TEX13A	ENST00000600991.6	TSL:1 MANE Select	c.428G>A	p.Arg143Lys	missense	Exon 2 of 3	ENSP00000471604.2	Q9BXU3
	TEX13A	ENST00000609007.3	TSL:1	c.428G>A	p.Arg143Lys	missense	Exon 2 of 3	ENSP00000477478.2	Q9BXU3
	IL1RAPL2	ENST00000372582.6	TSL:1 MANE Select	c.357-13848C>T		intron	N/A	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD2 exomes AF: 0.00000590 AC: 1 AN: 169567 AF XY: 0.0000174

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000130

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000368 AC: 4 AN: 1085689 Hom.: 0 Cov.: 31 AF XY: 0.00000282 AC XY: 1 AN XY: 354375

African (AFR) AF: 0.00 AC: 0 AN: 26205

American (AMR) AF: 0.00 AC: 0 AN: 34657

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18677

East Asian (EAS) AF: 0.00 AC: 0 AN: 30071

South Asian (SAS) AF: 0.00 AC: 0 AN: 52489

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38327

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4087

European-Non Finnish (NFE) AF: 0.00000479 AC: 4 AN: 835615

Other (OTH) AF: 0.00 AC: 0 AN: 45561

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000826 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.4
DANN	Benign	0.78
DEOGEN2	Benign	0.12	T
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.066	T
MetaSVM	Benign	-1.0	T
PhyloP100		0.93
PrimateAI	Benign	0.37	T
Sift4G	Benign	0.11	T
Polyphen		0.078	B
Vest4		0.36
MutPred		0.33		Gain of ubiquitination at R143 (P = 0.0085)
MVP		0.030
ClinPred		0.031	T
GERP RS		-0.073
Varity_R		0.052
gMVP		0.15
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs782792744; hg19: chrX-104464654; COSMIC: COSV61163592;