Variant chr10-125661848-T-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.181A>G(p.Lys61Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,551,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000086 ( 0 hom. )

Consequence

TEX36
NM_001128202.3 missense, splice_region

Scores

Splicing: ADA: 0.0009458

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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=0.17618936).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
TEX36	NM_001128202.3 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4	ENST00000368821.4
TEX36	NM_001318133.2 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4
TEX36	XM_005269817.5 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
TEX36	ENST00000368821.4 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4	1	NM_001128202.3	P1
TEX36	ENST00000532135.5 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4	1
TEX36	ENST00000526819.5 linkuse as main transcript	c.181A>G	p.Lys61Glu	missense_variant, splice_region_variant	2/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152200

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000857

AC:

AN:

1399488

Hom.:

Cov.:

AF XY:

0.00000869

AC XY:

AN XY:

690246

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:

0.00000834

Gnomad4 OTH exome

AF:

0.0000517

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74348

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:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000227

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 28, 2023

The c.181A>G (p.K61E) alteration is located in exon 2 (coding exon 2) of the TEX36 gene. This alteration results from a A to G substitution at nucleotide position 181, causing the lysine (K) at amino acid position 61 to be replaced by a glutamic acid (E). 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

0.16

BayesDel_addAF

Benign

-0.063

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

T;.;T

Eigen

Benign

0.080

Eigen_PC

Benign

0.085

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.74

T;T;T

M_CAP

Benign

0.035

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-0.69

MutationTaster

Benign

0.66

D;D

PrimateAI

Uncertain

0.48

PROVEAN

Uncertain

-3.1

D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.0090

D;D;D

Sift4G

Uncertain

0.010

D;D;D

Polyphen

0.70

P;.;P

Vest4

0.27

MutPred

0.38

Loss of methylation at K61 (P = 0.0057);Loss of methylation at K61 (P = 0.0057);Loss of methylation at K61 (P = 0.0057);

MVP

0.13

ClinPred

0.96

GERP RS

3.1

Varity_R

0.24

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00095

dbscSNV1_RF

Benign

0.022

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