6-52750617-T-G

Variant names:

• chr6-52750617-T-G
• rs6577
• NM_000846.5:c.629A>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.629A>C​(p.Glu210Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0858 in 1,613,556 control chromosomes in the GnomAD database, including 18,704 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 0.22 (8405 hom., cov: 33)
  • Exomes 𝑓: 0.072 (10299 hom.)
• Consequence: GSTA2 NM_000846.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26
• Publications: 34 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=4.5818906E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000846.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA2	NM_000846.5	MANE Select	c.629A>C	p.Glu210Ala	missense	Exon 7 of 7	NP_000837.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTA2	ENST00000493422.3	TSL:1 MANE Select	c.629A>C	p.Glu210Ala	missense	Exon 7 of 7	ENSP00000420168.1
	ENSG00000301390	ENST00000778609.1		n.72+4479T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33578 AN: 152068 Hom.: 8363 Cov.: 33

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0994

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.0538

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.106 AC: 26574 AN: 251346 AF XY: 0.0943

Gnomad AFR exome AF: 0.630

Gnomad AMR exome AF: 0.0647

Gnomad ASJ exome AF: 0.0958

Gnomad EAS exome AF: 0.162

Gnomad FIN exome AF: 0.0564

Gnomad NFE exome AF: 0.0546

Gnomad OTH exome AF: 0.0847

GnomAD4 exome AF: 0.0717 AC: 104802 AN: 1461370 Hom.: 10299 Cov.: 31 AF XY: 0.0703 AC XY: 51093 AN XY: 726982

African (AFR) AF: 0.649 AC: 21695 AN: 33452

American (AMR) AF: 0.0694 AC: 3102 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 2422 AN: 26130

East Asian (EAS) AF: 0.172 AC: 6831 AN: 39684

South Asian (SAS) AF: 0.0731 AC: 6306 AN: 86254

European-Finnish (FIN) AF: 0.0513 AC: 2742 AN: 53408

Middle Eastern (MID) AF: 0.163 AC: 920 AN: 5636

European-Non Finnish (NFE) AF: 0.0490 AC: 54514 AN: 1111740

Other (OTH) AF: 0.104 AC: 6270 AN: 60350

GnomAD4 genome AF: 0.221 AC: 33671 AN: 152186 Hom.: 8405 Cov.: 33 AF XY: 0.217 AC XY: 16132 AN XY: 74404

African (AFR) AF: 0.617 AC: 25571 AN: 41452

American (AMR) AF: 0.112 AC: 1718 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0994 AC: 345 AN: 3472

East Asian (EAS) AF: 0.170 AC: 878 AN: 5178

South Asian (SAS) AF: 0.0855 AC: 413 AN: 4828

European-Finnish (FIN) AF: 0.0569 AC: 604 AN: 10618

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.0538 AC: 3659 AN: 68032

Other (OTH) AF: 0.182 AC: 384 AN: 2112

Alfa AF: 0.131 Hom.: 2361

Bravo AF: 0.243

TwinsUK AF: 0.0485 AC: 180

ALSPAC AF: 0.0462 AC: 178

ESP6500AA AF: 0.601 AC: 2648

ESP6500EA AF: 0.0571 AC: 491

ExAC AF: 0.115 AC: 13966

Asia WGS AF: 0.136 AC: 472 AN: 3474

EpiCase AF: 0.0622

EpiControl AF: 0.0577

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.052
DANN	Benign	0.63
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.0083	T
MetaRNN	Benign	0.0000046	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.84	L
PhyloP100		-1.3
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.015
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Polyphen		0.0	B
Vest4		0.035
MPC		0.019
ClinPred		0.0050	T
GERP RS		-0.13
Varity_R		0.087
gMVP		0.26
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: rs6577; hg19: chr6-52615415; COSMIC: COSV72414734;