Genetic Variant TEX13A:p.Arg143Thr (chrX-105219970-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031274.5(TEX13A):c.428G>C(p.Arg143Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 112,750 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R143K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 9.2e-7 ( 0 hom. 1 hem. )

Failed GnomAD Quality Control

Consequence

TEX13A
NM_031274.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.933

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24853921).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX13A	NM_031274.5 link	c.428G>C	p.Arg143Thr	missense_variant	Exon 2 of 3	ENST00000600991.6	NP_112564.1	Q9BXU3
IL1RAPL2	NM_017416.2 link	c.357-13848C>G		intron_variant	Intron 3 of 10	ENST00000372582.6	NP_059112.1	Q9NP60
TEX13A	NM_001291277.2 link	c.428G>C	p.Arg143Thr	missense_variant	Exon 2 of 3		NP_001278206.1	Q9BXU3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX13A	ENST00000600991.6 link	c.428G>C	p.Arg143Thr	missense_variant	Exon 2 of 3	1	NM_031274.5	ENSP00000471604.2	Q9BXU3
TEX13A	ENST00000609007.3 link	c.428G>C	p.Arg143Thr	missense_variant	Exon 2 of 3	1		ENSP00000477478.2	Q9BXU3
IL1RAPL2	ENST00000372582.6 link	c.357-13848C>G		intron_variant	Intron 3 of 10	1	NM_017416.2	ENSP00000361663.1	Q9NP60

Frequencies

GnomAD3 genomes

AF:

0.00000887

AC:

AN:

112750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34896

show subpopulations

Gnomad AFR

AF:

0.0000322

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

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

9.21e-7

AC:

AN:

1085689

Hom.:

Cov.:

AF XY:

0.00000282

AC XY:

AN XY:

354375

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000333

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000887

AC:

AN:

112750

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34896

show subpopulations

Gnomad4 AFR

AF:

0.0000322

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

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.9

DANN

Benign

0.88

DEOGEN2

Benign

0.37

T;T

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.58

.;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.36

Sift4G

Uncertain

0.022

D;D

Polyphen

0.84

P;P

Vest4

0.51

MutPred

0.28

Gain of phosphorylation at R143 (P = 0.0441);Gain of phosphorylation at R143 (P = 0.0441);

MVP

0.055

ClinPred

0.22

GERP RS

-0.073

Varity_R

0.068

gMVP

0.22

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over