rs512795

Variant names:

• chr6-52902185-T-C
• rs512795
• NM_000847.5:c.272+161A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000847.5(GSTA3):​c.272+161A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,068 control chromosomes in the GnomAD database, including 9,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (9430 hom., cov: 32)
• Consequence: GSTA3 NM_000847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 7 publications found

Genes affected

GSTA3 (HGNC:4628): (glutathione S-transferase alpha 3) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. These enzymes are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. 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 genes that are located in a cluster mapped to chromosome 6. Genes of the alpha class are highly related and encode enzymes with glutathione peroxidase activity. However, during evolution, this alpha class gene diverged accumulating mutations in the active site that resulted in differences in substrate specificity and catalytic activity. The enzyme encoded by this gene catalyzes the double bond isomerization of precursors for progesterone and testosterone during the biosynthesis of steroid hormones. An additional transcript variant has been identified, but its full length sequence has not been determined. [provided by RefSeq, Jul 2008]

ENSG00000309866 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA3	NM_000847.5	c.272+161A>G		intron_variant	Intron 4 of 6	ENST00000211122.4	NP_000838.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTA3	ENST00000211122.4	c.272+161A>G		intron_variant	Intron 4 of 6	1	NM_000847.5	ENSP00000211122.3
GSTA3	ENST00000370968.5	c.122+161A>G		intron_variant	Intron 3 of 5	1		ENSP00000360007.1
GSTA3	ENST00000431899.2	c.122+161A>G		intron_variant	Intron 2 of 3	5		ENSP00000399142.2
ENSG00000309866	ENST00000844508.1	n.439-6722T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.268 AC: 40765 AN: 151950 Hom.: 9384 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.190

Gnomad FIN AF: 0.0660

Gnomad MID AF: 0.212

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.246

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.269 AC: 40860 AN: 152068 Hom.: 9430 Cov.: 32 AF XY: 0.271 AC XY: 20158 AN XY: 74340

African (AFR) AF: 0.596 AC: 24709 AN: 41454

American (AMR) AF: 0.376 AC: 5734 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 524 AN: 3468

East Asian (EAS) AF: 0.390 AC: 2013 AN: 5162

South Asian (SAS) AF: 0.189 AC: 910 AN: 4810

European-Finnish (FIN) AF: 0.0660 AC: 700 AN: 10608

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.0818 AC: 5562 AN: 67982

Other (OTH) AF: 0.242 AC: 512 AN: 2112

Alfa AF: 0.150 Hom.: 5975

Bravo AF: 0.307

Asia WGS AF: 0.325 AC: 1128 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.5
DANN	Benign	0.44
PhyloP100		-0.78
Mutation Taster		=100/0	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: rs512795; hg19: chr6-52766983; COSMIC: COSV52980266;