rs557135

Variant names:

• chr6-52900962-A-G
• rs557135
• NM_000847.5:c.273-887T>C

Variant summary

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

The NM_000847.5(GSTA3):​c.273-887T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,018 control chromosomes in the GnomAD database, including 17,365 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 0.46 (17365 hom., cov: 32)
• Consequence: GSTA3 NM_000847.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 9 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.64 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTA3	NM_000847.5	c.273-887T>C		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.273-887T>C		intron_variant	Intron 4 of 6	1	NM_000847.5	ENSP00000211122.3
GSTA3	ENST00000370968.5	c.123-887T>C		intron_variant	Intron 3 of 5	1		ENSP00000360007.1
GSTA3	ENST00000431899.2	c.123-887T>C		intron_variant	Intron 2 of 3	5		ENSP00000399142.2
ENSG00000309866	ENST00000844508.1	n.439-7945A>G		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.455 AC: 69178 AN: 151900 Hom.: 17322 Cov.: 32

Gnomad AFR AF: 0.647

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.476

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.464

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

GnomAD4 genome AF: 0.456 AC: 69264 AN: 152018 Hom.: 17365 Cov.: 32 AF XY: 0.456 AC XY: 33872 AN XY: 74312

African (AFR) AF: 0.647 AC: 26814 AN: 41452

American (AMR) AF: 0.569 AC: 8695 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1572 AN: 3468

East Asian (EAS) AF: 0.475 AC: 2458 AN: 5172

South Asian (SAS) AF: 0.334 AC: 1607 AN: 4810

European-Finnish (FIN) AF: 0.299 AC: 3154 AN: 10564

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.345 AC: 23462 AN: 67972

Other (OTH) AF: 0.458 AC: 968 AN: 2112

Alfa AF: 0.396 Hom.: 39811

Bravo AF: 0.486

Asia WGS AF: 0.424 AC: 1475 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.10
DANN	Benign	0.48
PhyloP100		-2.2
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: rs557135; hg19: chr6-52765760;