Variant 17-64193751-C-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_001288732.2(TEX2):c.1984G>A(p.Ala662Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000021 ( 0 hom. )

Consequence

TEX2
NM_001288732.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.60

Variant links:

Genes affected

TEX2 (HGNC:30884): (testis expressed 2) Predicted to enable lipid binding activity. Predicted to be involved in lipid transport. Predicted to be located in endoplasmic reticulum membrane and nuclear membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

TEX2 links:

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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=0.061166346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TEX2	NM_001288732.2 linkuse as main transcript	c.1984G>A	p.Ala662Thr	missense_variant	4/12	ENST00000584379.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TEX2	ENST00000584379.6 linkuse as main transcript	c.1984G>A	p.Ala662Thr	missense_variant	4/12	1	NM_001288732.2	P1	Q8IWB9-1
TEX2	ENST00000258991.7 linkuse as main transcript	c.1984G>A	p.Ala662Thr	missense_variant	4/12	1			Q8IWB9-2
TEX2	ENST00000583097.5 linkuse as main transcript	c.1984G>A	p.Ala662Thr	missense_variant	4/12	1		P1	Q8IWB9-1
TEX2	ENST00000583501.1 linkuse as main transcript	c.487G>A	p.Ala163Thr	missense_variant	3/11	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461590

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727112

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:

0.00000180

Gnomad4 OTH exome

AF:

0.0000166

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

Sep 29, 2022

The c.1984G>A (p.A662T) alteration is located in exon 4 (coding exon 3) of the TEX2 gene. This alteration results from a G to A substitution at nucleotide position 1984, causing the alanine (A) at amino acid position 662 to be replaced by a threonine (T). 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

0.072

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.70

Eigen

Benign

-0.91

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.48

T;.;T;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.31

N;.;.;.

REVEL

Benign

0.026

Sift

Benign

0.34

T;.;.;.

Sift4G

Benign

0.67

T;T;T;T

Polyphen

0.018

B;B;.;B

Vest4

0.12

MutPred

0.19

Gain of phosphorylation at A662 (P = 0.0019);Gain of phosphorylation at A662 (P = 0.0019);Gain of phosphorylation at A662 (P = 0.0019);Gain of phosphorylation at A662 (P = 0.0019);

MVP

0.11

MPC

0.30

ClinPred

0.094

GERP RS

0.94

Varity_R

0.018

gMVP

0.19

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over