rs36120609

chr1-109737630-ATCC-Achr1-109737630-ATCC-ATCCTCC

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000849.5(GSTM3):c.468+23_468+25del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,514,644 control chromosomes in the GnomAD database, including 31,890 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.27 (9090 hom., cov: 24)
  • Exomes 𝑓: 0.16 (22800 hom.)
• Consequence: GSTM3 NM_000849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.443

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]

(HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM3	NM_000849.5	c.468+23_468+25del		intron_variant		ENST00000361066.7
GSTM3	NR_024537.2	n.702+23_702+25del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM3	ENST00000361066.7	c.468+23_468+25del		intron_variant		1	NM_000849.5	P1
	ENST00000431955.1	n.627+492_627+494del		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41665 AN: 151872 Hom.: 9069 Cov.: 24

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.178

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.245

GnomAD3 exomes AF: 0.163 AC: 40208 AN: 246230 Hom.: 5357 AF XY: 0.156 AC XY: 20759 AN XY: 133228

Gnomad AFR exome AF: 0.623

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.190

Gnomad EAS exome AF: 0.000877

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.159

Gnomad OTH exome AF: 0.153

GnomAD4 exome AF: 0.164 AC: 222895 AN: 1362654 Hom.: 22800 AF XY: 0.161 AC XY: 109972 AN XY: 682962

Gnomad4 AFR exome AF: 0.645

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.193

Gnomad4 EAS exome AF: 0.000739

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.134

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.178

GnomAD4 genome AF: 0.274 AC: 41719 AN: 151990 Hom.: 9090 Cov.: 24 AF XY: 0.269 AC XY: 19998 AN XY: 74340

Gnomad4 AFR AF: 0.611

Gnomad4 AMR AF: 0.161

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.243

Alfa AF: 0.219 Hom.: 958

Bravo AF: 0.290

Asia WGS AF: 0.0950 AC: 333 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs36120609; hg19: chr1-110280252;