Genetic Variant GSTA5:p.Glu210Gln (chr6-52831889-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_153699.3(GSTA5):c.628G>C(p.Glu210Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0000041 ( 0 hom. )

Consequence

GSTA5
NM_153699.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.55

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_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0631538).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA5	NM_153699.3 link	c.628G>C	p.Glu210Gln	missense_variant	Exon 6 of 6		NP_714543.1	Q7RTV2
GSTA5	XM_054328422.1 link	c.628G>C	p.Glu210Gln	missense_variant	Exon 7 of 7		XP_054184397.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA5	ENST00000370989.6 link	c.628G>C	p.Glu210Gln	missense_variant	Exon 6 of 6	1		ENSP00000360028.1		Q7RTV2
GSTA5	ENST00000475052.1 link	n.525G>C		non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000518828.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251256

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

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:

0.00000410

AC:

AN:

1461682

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727108

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.628G>C (p.E210Q) alteration is located in exon 7 (coding exon 6) of the GSTA5 gene. This alteration results from a G to C substitution at nucleotide position 628, causing the glutamic acid (E) at amino acid position 210 to be replaced by a glutamine (Q). 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

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.2

DANN

Benign

0.92

DEOGEN2

Benign

0.027

T;T

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.57

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.014

.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.063

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.4

M;M

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

N;N

REVEL

Benign

0.070

Sift

Benign

0.051

T;T

Sift4G

Benign

0.088

T;T

Polyphen

0.0020

B;B

Vest4

0.077

MutPred

0.28

Loss of ubiquitination at K211 (P = 0.0274);Loss of ubiquitination at K211 (P = 0.0274);

MVP

0.31

MPC

0.0094

ClinPred

0.066

GERP RS

2.5

Varity_R

0.061

gMVP

0.27

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