Variant X-105220376-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000600991.6(TEX13A):c.22C>A(p.Pro8Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,188,667 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 9 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 0.000036 ( 0 hom., 1 hem., cov: 23)

Exomes 𝑓: 0.000019 ( 0 hom. 8 hem. )

Consequence

TEX13A
ENST00000600991.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.471

Variant links:

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]

TEX13A links:

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]

IL1RAPL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044526488).

BS2

High Hemizygotes in GnomAdExome4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TEX13A	NM_031274.5 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	2/3	ENST00000600991.6	NP_112564.1
IL1RAPL2	NM_017416.2 linkuse as main transcript	c.357-13442G>T		intron_variant		ENST00000372582.6	NP_059112.1
TEX13A	NM_001291277.2 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	2/3		NP_001278206.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
TEX13A	ENST00000600991.6 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	2/3	1	NM_031274.5	ENSP00000471604	P1
TEX13A	ENST00000609007.3 linkuse as main transcript	c.22C>A	p.Pro8Thr	missense_variant	2/3	1		ENSP00000477478	P1
IL1RAPL2	ENST00000372582.6 linkuse as main transcript	c.357-13442G>T		intron_variant		1	NM_017416.2	ENSP00000361663	P1

Frequencies

GnomAD3 genomes

AF:

0.0000359

AC:

AN:

111351

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33547

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000755

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000195

AC:

AN:

1077316

Hom.:

Cov.:

AF XY:

0.0000230

AC XY:

AN XY:

348380

show subpopulations

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:

0.0000241

Gnomad4 OTH exome

AF:

0.0000221

GnomAD4 genome

AF:

0.0000359

AC:

AN:

111351

Hom.:

Cov.:

AF XY:

0.0000298

AC XY:

AN XY:

33547

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000755

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.00000825

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.22C>A (p.P8T) alteration is located in exon 2 (coding exon 1) of the TEX13A gene. This alteration results from a C to A substitution at nucleotide position 22, causing the proline (P) at amino acid position 8 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

0.11

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.93

CADD

Benign

1.4

DANN

Benign

0.66

DEOGEN2

Benign

0.048

T;T

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.55

.;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.33

Sift4G

Benign

0.97

T;T

Polyphen

0.030

B;B

Vest4

0.14

MutPred

0.23

Gain of relative solvent accessibility (P = 0.0479);Gain of relative solvent accessibility (P = 0.0479);

MVP

0.014

ClinPred

0.048

GERP RS

0.72

Varity_R

0.054

gMVP

0.090

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over