Variant 9-100303781-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000374902.9(TEX10):c.2527A>G(p.Met843Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00143 in 1,614,016 control chromosomes in the GnomAD database, including 3 homozygotes. 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 0.0013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 3 hom. )

Consequence

TEX10
ENST00000374902.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

TEX10 (HGNC:25988): (testis expressed 10) Located in mitochondrion and nucleoplasm. Part of MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

TEX10 links:

TEX10 (HGNC:):

TEX10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008844703).

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX10	NM_017746.4 linkuse as main transcript	c.2527A>G	p.Met843Val	missense_variant	14/15	ENST00000374902.9	NP_060216.2	Q9NXF1-1A0A024R169
TEX10	NM_001161584.2 linkuse as main transcript	c.2479A>G	p.Met827Val	missense_variant	14/15		NP_001155056.1	Q9NXF1-2
TEX10	XM_011518798.3 linkuse as main transcript	c.2152A>G	p.Met718Val	missense_variant	12/13		XP_011517100.1
TEX10	XM_047423523.1 linkuse as main transcript	c.2345A>G	p.Asp782Gly	missense_variant	13/13		XP_047279479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TEX10	ENST00000374902.9 linkuse as main transcript	c.2527A>G	p.Met843Val	missense_variant	14/15	1	NM_017746.4	ENSP00000364037.4	Q9NXF1-1
TEX10	ENST00000535814.5 linkuse as main transcript	c.2479A>G	p.Met827Val	missense_variant	14/15	2		ENSP00000444555.1	Q9NXF1-2
TEX10	ENST00000477648.1 linkuse as main transcript	n.4089A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152010

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00190

Gnomad OTH

AF:

0.00385

GnomAD3 exomes

AF:

0.00111

AC:

279

AN:

250748

Hom.:

AF XY:

0.00103

AC XY:

140

AN XY:

135582

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.000954

Gnomad ASJ exome

AF:

0.00656

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00145

AC:

2114

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00136

AC XY:

986

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000225

Gnomad4 NFE exome

AF:

0.00161

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00128

AC:

195

AN:

152128

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.000458

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00190

Gnomad4 OTH

AF:

0.00381

Alfa

AF:

0.00167

Hom.:

Bravo

AF:

0.00120

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00109

AC:

132

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00166

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

Feb 16, 2023

The c.2527A>G (p.M843V) alteration is located in exon 14 (coding exon 13) of the TEX10 gene. This alteration results from a A to G substitution at nucleotide position 2527, causing the methionine (M) at amino acid position 843 to be replaced by a valine (V). 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

0.26

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Uncertain

0.060

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.040

.;T

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0033

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.25

N;N

REVEL

Benign

0.16

Sift

Benign

0.43

T;T

Sift4G

Benign

0.69

T;T

Polyphen

0.15

.;B

Vest4

0.35

MVP

0.44

MPC

0.33

ClinPred

0.0068

GERP RS

4.9

Varity_R

0.10

gMVP

0.28

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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