Variant 10-125656003-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001128202.3(TEX36):c.458C>A(p.Ala153Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000786 in 1,399,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

TEX36
NM_001128202.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.238

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06643).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX36	NM_001128202.3 link	c.458C>A	p.Ala153Asp	missense_variant	4/4	ENST00000368821.4	NP_001121674.1	Q5VZQ5
TEX36	NM_001318133.2 link	c.264+5018C>A		intron_variant			NP_001305062.1	Q5VZQ5A0PJZ8E9PJL2
TEX36	XM_005269817.5 link	c.264+5018C>A		intron_variant			XP_005269874.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX36	ENST00000368821.4 link	c.458C>A	p.Ala153Asp	missense_variant	4/4	1	NM_001128202.3	ENSP00000357811.3	Q5VZQ5
TEX36	ENST00000532135.5 link	c.264+5018C>A		intron_variant		1		ENSP00000431764.1	E9PJL2
TEX36	ENST00000526819.5 link	c.264+5018C>A		intron_variant		5		ENSP00000434299.1	E9PR91

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000634

AC:

AN:

157816

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83298

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:

0.0000163

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000786

AC:

AN:

1399586

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

690258

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:

0.00000927

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

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

Nov 15, 2024

The c.458C>A (p.A153D) alteration is located in exon 4 (coding exon 4) of the TEX36 gene. This alteration results from a C to A substitution at nucleotide position 458, causing the alanine (A) at amino acid position 153 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.62

CADD

Benign

5.9

DANN

Benign

0.79

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.30

M_CAP

Benign

0.011

MetaRNN

Benign

0.066

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.20

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.0

REVEL

Benign

0.052

Sift

Benign

0.36

Sift4G

Benign

0.47

Polyphen

0.0

Vest4

0.12

MutPred

0.39

Loss of helix (P = 0.0196);

MVP

0.21

ClinPred

0.037

GERP RS

0.69

Varity_R

0.078

gMVP

0.20

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