Variant 9-100329269-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_017746.4(TEX10):c.1496C>T(p.Thr499Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000346 in 1,444,108 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: not found (cov: 32)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TEX10
NM_017746.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.50

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.4206176).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TEX10	NM_017746.4 linkuse as main transcript	c.1496C>T	p.Thr499Ile	missense_variant	7/15	ENST00000374902.9	NP_060216.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TEX10	ENST00000374902.9 linkuse as main transcript	c.1496C>T	p.Thr499Ile	missense_variant	7/15	1	NM_017746.4	ENSP00000364037	P1	Q9NXF1-1
TEX10	ENST00000535814.5 linkuse as main transcript	c.1505C>T	p.Thr502Ile	missense_variant	7/15	2		ENSP00000444555		Q9NXF1-2
TEX10	ENST00000429235.1 linkuse as main transcript	c.431C>T	p.Thr144Ile	missense_variant	5/5	5		ENSP00000399872

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000214

AC:

AN:

233810

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

126374

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000172

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000346

AC:

AN:

1444108

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000104

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:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Jun 03, 2022

The c.1496C>T (p.T499I) alteration is located in exon 7 (coding exon 6) of the TEX10 gene. This alteration results from a C to T substitution at nucleotide position 1496, causing the threonine (T) at amino acid position 499 to be replaced by an isoleucine (I). 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

0.29

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.076

.;T;T

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.65

T;T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.42

T;T;T

MetaSVM

Benign

-0.59

MutationAssessor

Benign

0.97

.;L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.5

N;N;D

REVEL

Benign

0.19

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.0050

D;D;.

Polyphen

0.31

.;B;.

Vest4

0.54

MutPred

0.71

.;Gain of helix (P = 0.0425);.;

MVP

0.093

MPC

0.41

ClinPred

0.45

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.20

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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