6-52752933-C-G

Position:

• chr6-52752933-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000846.5(GSTA2):​c.335G>C​(p.Ser112Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,613,478 control chromosomes in the GnomAD database, including 282,524 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.53 (22476 hom., cov: 32)
  • Exomes 𝑓: 0.59 (260048 hom.)
• Consequence: GSTA2 NM_000846.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.28

Genes affected

GSTA2 (HGNC:4627): (glutathione S-transferase alpha 2) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes function in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding these enzymes are known to be highly polymorphic. These genetic variations can change an individual's susceptibility to carcinogens and toxins as well as affect the toxicity and efficacy of some drugs. At present, eight distinct classes of the soluble cytoplasmic mammalian glutathione S-transferases have been identified: alpha, kappa, mu, omega, pi, sigma, theta and zeta. This gene encodes a glutathione S-tranferase belonging to the alpha class. The alpha class genes, located in a cluster mapped to chromosome 6, are the most abundantly expressed glutathione S-transferases in liver. In addition to metabolizing bilirubin and certain anti-cancer drugs in the liver, the alpha class of these enzymes exhibit glutathione peroxidase activity thereby protecting the cells from reactive oxygen species and the products of peroxidation. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.8149684E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTA2	NM_000846.5	c.335G>C	p.Ser112Thr	missense_variant	5/7	ENST00000493422.3
GSTA2	XM_047418684.1	c.335G>C	p.Ser112Thr	missense_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTA2	ENST00000493422.3	c.335G>C	p.Ser112Thr	missense_variant	5/7	1	NM_000846.5	P1

Frequencies

GnomAD3 genomes AF: 0.527 AC: 80035 AN: 151930 Hom.: 22469 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.711

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.524

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.544

GnomAD3 exomes AF: 0.601 AC: 151056 AN: 251286 Hom.: 46895 AF XY: 0.599 AC XY: 81389 AN XY: 135802

Gnomad AFR exome AF: 0.315

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.515

Gnomad EAS exome AF: 0.714

Gnomad SAS exome AF: 0.592

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.593

Gnomad OTH exome AF: 0.598

GnomAD4 exome AF: 0.593 AC: 866812 AN: 1461430 Hom.: 260048 Cov.: 40 AF XY: 0.593 AC XY: 431013 AN XY: 727022

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.747

Gnomad4 ASJ exome AF: 0.511

Gnomad4 EAS exome AF: 0.702

Gnomad4 SAS exome AF: 0.589

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.596

Gnomad4 OTH exome AF: 0.582

GnomAD4 genome AF: 0.527 AC: 80063 AN: 152048 Hom.: 22476 Cov.: 32 AF XY: 0.531 AC XY: 39459 AN XY: 74318

Gnomad4 AFR AF: 0.322

Gnomad4 AMR AF: 0.669

Gnomad4 ASJ AF: 0.524

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.562

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.549

Alfa AF: 0.582 Hom.: 19593

Bravo AF: 0.528

TwinsUK AF: 0.594 AC: 2202

ALSPAC AF: 0.602 AC: 2322

ESP6500AA AF: 0.328 AC: 1445

ESP6500EA AF: 0.589 AC: 5062

ExAC AF: 0.592 AC: 71827

Asia WGS AF: 0.635 AC: 2208 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.580

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.045
DANN	Benign	0.22
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0058	N
LIST_S2	Benign	0.0027	T
MetaRNN	Benign	0.0000028	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.28	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.17	N
REVEL	Benign	0.0070
Sift	Benign	0.65	T
Sift4G	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.029
MPC		0.019
ClinPred		0.0028	T
GERP RS		-4.5
Varity_R		0.11
gMVP		0.077

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

Other links and lift over

dbSNP: rs2180314; hg19: chr6-52617731; COSMIC: COSV72414982;