chr1-109737199-C-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.580-30G>T		intron_variant	Intron 8 of 8	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.814-30G>T		intron_variant	Intron 7 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7	c.580-30G>T		intron_variant	Intron 8 of 8	1	NM_000849.5	ENSP00000354357.2

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

GnomAD3 exomes AF: 0.472 AC: 118123 AN: 250030 Hom.: 30558 AF XY: 0.475 AC XY: 64217 AN XY: 135270

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 SAS exome AF: 0.576

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

Gnomad4 AFR exome AF: 0.191

Gnomad4 AMR exome AF: 0.556

Gnomad4 ASJ exome AF: 0.347

Gnomad4 EAS exome AF: 0.832

Gnomad4 SAS exome AF: 0.573

Gnomad4 FIN exome AF: 0.418

Gnomad4 NFE exome AF: 0.427

Gnomad4 OTH exome AF: 0.440

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

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.468

Gnomad4 ASJ AF: 0.347

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.578

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.381

Alfa AF: 0.398 Hom.: 7666

Bravo AF: 0.383

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.4
DANN	Benign	0.65

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

Publications

LitVar

Other links and lift over

dbSNP: rs1537234; hg19: chr1-110279821;