X-105220384-G-C

Variant names:

• chrX-105220384-G-C
• rs1245997299
• NM_031274.5:c.14C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_031274.5(TEX13A):​c.14C>G​(p.Pro5Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000152 in 1,185,313 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., 2 hem., cov: 22)
  • Exomes 𝑓: 0.0000056 (0 hom. 2 hem.)
• Consequence: TEX13A NM_031274.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.858

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 -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3280998).
• BS2: High Hemizygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX13A	NM_031274.5	c.14C>G	p.Pro5Arg	missense_variant	Exon 2 of 3	ENST00000600991.6	NP_112564.1
IL1RAPL2	NM_017416.2	c.357-13434G>C		intron_variant	Intron 3 of 10	ENST00000372582.6	NP_059112.1
TEX13A	NM_001291277.2	c.14C>G	p.Pro5Arg	missense_variant	Exon 2 of 3		NP_001278206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TEX13A	ENST00000600991.6	c.14C>G	p.Pro5Arg	missense_variant	Exon 2 of 3	1	NM_031274.5	ENSP00000471604.2
TEX13A	ENST00000609007.3	c.14C>G	p.Pro5Arg	missense_variant	Exon 2 of 3	1		ENSP00000477478.2
IL1RAPL2	ENST00000372582.6	c.357-13434G>C		intron_variant	Intron 3 of 10	1	NM_017416.2	ENSP00000361663.1

Frequencies

GnomAD3 genomes AF: 0.000108 AC: 12 AN: 111438 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.0000653

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000948

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

GnomAD4 exome AF: 0.00000559 AC: 6 AN: 1073875 Hom.: 0 Cov.: 31 AF XY: 0.00000577 AC XY: 2 AN XY: 346529

African (AFR) AF: 0.00 AC: 0 AN: 26016

American (AMR) AF: 0.000147 AC: 5 AN: 33949

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17735

East Asian (EAS) AF: 0.00 AC: 0 AN: 29941

South Asian (SAS) AF: 0.00 AC: 0 AN: 50192

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38978

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3837

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 828240

Other (OTH) AF: 0.0000222 AC: 1 AN: 44987

GnomAD4 genome AF: 0.000108 AC: 12 AN: 111438 Hom.: 0 Cov.: 22 AF XY: 0.0000595 AC XY: 2 AN XY: 33626

African (AFR) AF: 0.0000653 AC: 2 AN: 30613

American (AMR) AF: 0.000948 AC: 10 AN: 10545

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2644

East Asian (EAS) AF: 0.00 AC: 0 AN: 3511

South Asian (SAS) AF: 0.00 AC: 0 AN: 2624

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6074

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53016

Other (OTH) AF: 0.00 AC: 0 AN: 1490

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000200

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.14C>G (p.P5R) alteration is located in exon 2 (coding exon 1) of the TEX13A gene. This alteration results from a C to G substitution at nucleotide position 14, causing the proline (P) at amino acid position 5 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	0.26
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T
FATHMM_MKL	Benign	0.057	N
LIST_S2	Benign	0.72	.;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.33	T;T
MetaSVM	Benign	-0.98	T
PhyloP100		0.86
PrimateAI	Benign	0.44	T
Sift4G	Uncertain	0.0030	D;D
Polyphen		1.0	D;D
Vest4		0.53
MutPred		0.16		Loss of glycosylation at P5 (P = 0.0715);Loss of glycosylation at P5 (P = 0.0715);
MVP		0.014
ClinPred		0.70	D
GERP RS		0.61
PromoterAI		-0.0082	Neutral
Varity_R		0.13
gMVP		0.14
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

dbSNP: rs1245997299; hg19: chrX-104465068;