rs1537234

Variant names:

• chr1-109737199-C-A
• rs1537234
• NM_000849.5:c.580-30G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-109737199-C-A
• chr1-109737199-C-G
• chr1-109737199-C-T

Variant summary

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

The NM_000849.5(GSTM3):​c.580-30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,469,816 control chromosomes in the GnomAD database, including 150,054 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 0.39 (12976 hom., cov: 32)
  • Exomes 𝑓: 0.45 (137078 hom.)
• Consequence: GSTM3 NM_000849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 17 publications found

Genes affected

GSTM3 (HGNC:4635): (glutathione S-transferase mu 3) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. 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-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and 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 certain drugs. Mutations of this class mu gene have been linked with a slight increase in a number of cancers, likely due to exposure with environmental toxins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) Cytosolic and membrane-bound forms of glutathione S-transferase are encoded by two distinct supergene families. 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-transferase that belongs to the mu class. The mu class of enzymes functions in the detoxification of electrophilic compounds, including carcinogens, therapeutic drugs, environmental toxins and products of oxidative stress, by conjugation with glutathione. The genes encoding the mu class of enzymes are organized in a gene cluster on chromosome 1p13.3 and 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 certain drugs. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

ENSG00000241720 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000849.5. 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
	GSTM3	NM_000849.5	MANE Select	c.580-30G>T		intron	N/A	NP_000840.2
	GSTM3	NR_024537.2		n.814-30G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.580-30G>T		intron	N/A	ENSP00000354357.2
	GSTM3	ENST00000256594.7	TSL:1	c.580-30G>T		intron	N/A	ENSP00000256594.3
	GSTM3	ENST00000476321.5	TSL:3	n.518G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58986 AN: 151950 Hom.: 12957 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.467

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.376

GnomAD2 exomes AF: 0.472 AC: 118123 AN: 250030 AF XY: 0.475

Gnomad AFR exome AF: 0.205

Gnomad AMR exome AF: 0.566

Gnomad ASJ exome AF: 0.345

Gnomad EAS exome AF: 0.848

Gnomad FIN exome AF: 0.414

Gnomad NFE exome AF: 0.418

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.445 AC: 586844 AN: 1317748 Hom.: 137078 Cov.: 20 AF XY: 0.449 AC XY: 298012 AN XY: 663576

African (AFR) AF: 0.191 AC: 5840 AN: 30540

American (AMR) AF: 0.556 AC: 24751 AN: 44506

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 8752 AN: 25206

East Asian (EAS) AF: 0.832 AC: 32540 AN: 39098

South Asian (SAS) AF: 0.573 AC: 47892 AN: 83518

European-Finnish (FIN) AF: 0.418 AC: 22314 AN: 53342

Middle Eastern (MID) AF: 0.355 AC: 1950 AN: 5490

European-Non Finnish (NFE) AF: 0.427 AC: 418322 AN: 980426

Other (OTH) AF: 0.440 AC: 24483 AN: 55622

GnomAD4 genome AF: 0.388 AC: 59043 AN: 152068 Hom.: 12976 Cov.: 32 AF XY: 0.393 AC XY: 29187 AN XY: 74314

African (AFR) AF: 0.209 AC: 8684 AN: 41476

American (AMR) AF: 0.468 AC: 7145 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3466

East Asian (EAS) AF: 0.842 AC: 4359 AN: 5174

South Asian (SAS) AF: 0.578 AC: 2789 AN: 4822

European-Finnish (FIN) AF: 0.421 AC: 4450 AN: 10560

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.428 AC: 29079 AN: 67978

Other (OTH) AF: 0.381 AC: 805 AN: 2112

Alfa AF: 0.406 Hom.: 11181

Bravo AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		0.11
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: rs1537234; hg19: chr1-110279821;