6-52752933-C-G

Variant names:

• chr6-52752933-C-G
• rs2180314
• NM_000846.5:c.335G>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 71 publications found

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]

ENSG00000301390 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GSTA2	NM_000846.5	c.335G>C	p.Ser112Thr	missense_variant	Exon 5 of 7	ENST00000493422.3	NP_000837.3
GSTA2	XM_047418684.1	c.335G>C	p.Ser112Thr	missense_variant	Exon 6 of 8		XP_047274640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA2	ENST00000493422.3	c.335G>C	p.Ser112Thr	missense_variant	Exon 5 of 7	1	NM_000846.5	ENSP00000420168.1
ENSG00000301390	ENST00000778609.1	n.73-6676C>G		intron_variant	Intron 1 of 1

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

GnomAD2 exomes AF: 0.601 AC: 151056 AN: 251286 AF XY: 0.599

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 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

African (AFR) AF: 0.299 AC: 10013 AN: 33466

American (AMR) AF: 0.747 AC: 33396 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 13337 AN: 26122

East Asian (EAS) AF: 0.702 AC: 27854 AN: 39686

South Asian (SAS) AF: 0.589 AC: 50789 AN: 86240

European-Finnish (FIN) AF: 0.570 AC: 30448 AN: 53406

Middle Eastern (MID) AF: 0.483 AC: 2781 AN: 5762

European-Non Finnish (NFE) AF: 0.596 AC: 663063 AN: 1111652

Other (OTH) AF: 0.582 AC: 35131 AN: 60376

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

African (AFR) AF: 0.322 AC: 13355 AN: 41442

American (AMR) AF: 0.669 AC: 10206 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.524 AC: 1818 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3640 AN: 5168

South Asian (SAS) AF: 0.585 AC: 2823 AN: 4822

European-Finnish (FIN) AF: 0.562 AC: 5941 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.593 AC: 40315 AN: 67990

Other (OTH) AF: 0.549 AC: 1160 AN: 2114

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
PhyloP100		-3.3
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
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

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