Genetic Variant TEX36:p.Arg59Gln (chr10-125661853-C-T) – 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_001128202.3(TEX36):c.176G>A(p.Arg59Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000226 in 1,551,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

TEX36
NM_001128202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Variant links:

Genes affected

TEX36 (HGNC:31653): (testis expressed 36)

TEX36 links:

Genome browser will be placed here

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=0.13255769).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TEX36	NM_001128202.3 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4	ENST00000368821.4	NP_001121674.1	Q5VZQ5
TEX36	NM_001318133.2 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4		NP_001305062.1	Q5VZQ5A0PJZ8E9PJL2
TEX36	XM_005269817.5 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4		XP_005269874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TEX36	ENST00000368821.4 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4	1	NM_001128202.3	ENSP00000357811.3	Q5VZQ5
TEX36	ENST00000532135.5 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4	1		ENSP00000431764.1	E9PJL2
TEX36	ENST00000526819.5 link	c.176G>A	p.Arg59Gln	missense_variant	Exon 2 of 4	5		ENSP00000434299.1	E9PR91

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000383

AC:

AN:

156486

Hom.:

AF XY:

0.0000482

AC XY:

AN XY:

82918

show subpopulations

Gnomad AFR exome

AF:

0.000126

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000917

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000662

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000200

AC:

AN:

1399504

Hom.:

Cov.:

AF XY:

0.0000217

AC XY:

AN XY:

690262

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000241

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152204

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000114

Hom.:

Bravo

AF:

0.0000453

ESP6500AA

AF:

0.000723

AC:

ESP6500EA

AF:

0.000314

AC:

ExAC

AF:

0.0000389

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Apr 28, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.176G>A (p.R59Q) alteration is located in exon 2 (coding exon 2) of the TEX36 gene. This alteration results from a G to A substitution at nucleotide position 176, causing the arginine (R) at amino acid position 59 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.11

T;.;T

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.79

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Uncertain

2.5

.;.;M

PrimateAI

Benign

0.36

PROVEAN

Uncertain

-2.8

D;D;N

REVEL

Benign

0.11

Sift

Uncertain

0.0090

D;D;T

Sift4G

Uncertain

0.015

D;T;T

Polyphen

0.97

D;.;P

Vest4

0.26

MVP

0.20

ClinPred

0.17

GERP RS

3.3

Varity_R

0.12

gMVP

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over