Variant 6-52840756-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000370989.7(GSTA5):c.58C>T(p.Arg20Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GSTA5
ENST00000370989.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.82

Variant links:

Genes affected

GSTA5 (HGNC:19662): (glutathione S-transferase alpha 5) The glutathione S-transferases (GST; EC 2.5.1.18) catalyze the conjugation of reduced glutathiones and a variety of electrophiles, including many known carcinogens and mutagens. The cytosolic GSTs belong to a large superfamily, with members located on different chromosomes. For additional information on GSTs, see GSTA1 (MIM 138359).[supplied by OMIM, Sep 2008]

GSTA5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.97

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA5	NM_153699.3 linkuse as main transcript	c.58C>T	p.Arg20Trp	missense_variant	1/6	ENST00000370989.7
GSTA5	XM_054328422.1 linkuse as main transcript	c.58C>T	p.Arg20Trp	missense_variant	2/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA5	ENST00000370989.7 linkuse as main transcript	c.58C>T	p.Arg20Trp	missense_variant	1/6	1	NM_153699.3	P1
GSTA5	ENST00000475052.2 linkuse as main transcript	c.58C>T	p.Arg20Trp	missense_variant, NMD_transcript_variant	1/5	5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461762

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727176

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:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jan 04, 2024

The c.58C>T (p.R20W) alteration is located in exon 2 (coding exon 1) of the GSTA5 gene. This alteration results from a C to T substitution at nucleotide position 58, causing the arginine (R) at amino acid position 20 to be replaced by a tryptophan (W). 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

0.33

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.20

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.046

T;T

Eigen

Benign

0.068

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.34

M_CAP

Benign

0.0096

MetaRNN

Pathogenic

0.97

D;D

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

4.7

H;H

MutationTaster

Benign

0.98

D;D

PrimateAI

Uncertain

0.61

PROVEAN

Pathogenic

-6.8

D;D

REVEL

Benign

0.25

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.010

D;D

Polyphen

1.0

D;D

Vest4

0.88

MutPred

0.84

Loss of disorder (P = 0.0318);Loss of disorder (P = 0.0318);

MVP

0.31

MPC

0.059

ClinPred

0.98

GERP RS

1.1

Varity_R

0.52

gMVP

0.87

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