Variant chr10-125656028-G-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001128202.3(TEX36):c.433C>G(p.Arg145Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000129 in 1,551,686 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TEX36
NM_001128202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.990

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=0.25690812).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX36	NM_001128202.3 linkuse as main transcript	c.433C>G	p.Arg145Gly	missense_variant	4/4	ENST00000368821.4	NP_001121674.1	Q5VZQ5
TEX36	NM_001318133.2 linkuse as main transcript	c.264+4993C>G		intron_variant			NP_001305062.1	Q5VZQ5A0PJZ8E9PJL2
TEX36	XM_005269817.5 linkuse as main transcript	c.264+4993C>G		intron_variant			XP_005269874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX36	ENST00000368821.4 linkuse as main transcript	c.433C>G	p.Arg145Gly	missense_variant	4/4	1	NM_001128202.3	ENSP00000357811.3	Q5VZQ5
TEX36	ENST00000532135.5 linkuse as main transcript	c.264+4993C>G		intron_variant		1		ENSP00000431764.1	E9PJL2
TEX36	ENST00000526819.5 linkuse as main transcript	c.264+4993C>G		intron_variant		5		ENSP00000434299.1	E9PR91

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151990

Hom.:

Cov.:

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000190

AC:

AN:

158132

Hom.:

AF XY:

0.0000240

AC XY:

AN XY:

83408

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000487

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1399696

Hom.:

Cov.:

AF XY:

0.0000174

AC XY:

AN XY:

690326

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:

0.0000202

Gnomad4 NFE exome

AF:

0.0000148

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74222

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:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000100

Hom.:

Bravo

AF:

0.0000302

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

Aug 14, 2023

The c.433C>G (p.R145G) alteration is located in exon 4 (coding exon 4) of the TEX36 gene. This alteration results from a C to G substitution at nucleotide position 433, causing the arginine (R) at amino acid position 145 to be replaced by a glycine (G). 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

0.30

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.064

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.69

M_CAP

Benign

0.027

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.86

MutationAssessor

Uncertain

2.6

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.2

REVEL

Benign

0.18

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.0060

Polyphen

0.98

Vest4

0.38

MutPred

0.34

Loss of MoRF binding (P = 0.0063);

MVP

0.48

ClinPred

0.95

GERP RS

1.6

Varity_R

0.25

gMVP

0.25

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