rs36120609

Variant names:

• chr1-109737630-ATCC-A
• rs36120609
• NM_000849.5:c.468+23_468+25delGGA

Your query was ambiguous. Multiple possible variants found:

• chr1-109737630-ATCC-A
• chr1-109737630-ATCC-ATCCTCC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000849.5(GSTM3):​c.468+23_468+25delGGA 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
• Publications: 5 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.605 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.468+23_468+25delGGA		intron	N/A	NP_000840.2
	GSTM3	NR_024537.2		n.702+23_702+25delGGA		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.468+23_468+25delGGA		intron	N/A	ENSP00000354357.2
	GSTM3	ENST00000256594.7	TSL:1	c.468+23_468+25delGGA		intron	N/A	ENSP00000256594.3
	GSTM5	ENST00000429410.2	TSL:2	n.82+25283_82+25285delTCC		intron	N/A

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

GnomAD2 exomes AF: 0.163 AC: 40208 AN: 246230 AF XY: 0.156

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 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

African (AFR) AF: 0.645 AC: 20393 AN: 31622

American (AMR) AF: 0.106 AC: 4657 AN: 43784

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 4873 AN: 25238

East Asian (EAS) AF: 0.000739 AC: 29 AN: 39234

South Asian (SAS) AF: 0.120 AC: 10036 AN: 83436

European-Finnish (FIN) AF: 0.134 AC: 7117 AN: 53266

Middle Eastern (MID) AF: 0.225 AC: 1255 AN: 5590

European-Non Finnish (NFE) AF: 0.161 AC: 164367 AN: 1023444

Other (OTH) AF: 0.178 AC: 10168 AN: 57040

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

African (AFR) AF: 0.611 AC: 25268 AN: 41334

American (AMR) AF: 0.161 AC: 2458 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.193 AC: 668 AN: 3468

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5188

South Asian (SAS) AF: 0.120 AC: 577 AN: 4828

European-Finnish (FIN) AF: 0.131 AC: 1383 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10605 AN: 67978

Other (OTH) AF: 0.243 AC: 513 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.44
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs36120609; hg19: chr1-110280252;