rs1571858

Variant names:

• chr1-109737292-C-T
• rs1571858
• NM_000849.5:c.580-123G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109737292-C-T
• chr1-109737292-C-A
• chr1-109737292-C-G

Variant summary

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

The NM_000849.5(GSTM3):​c.580-123G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 816,990 control chromosomes in the GnomAD database, including 49,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.28 (7068 hom., cov: 33)
  • Exomes 𝑓: 0.34 (42542 hom.)
• Consequence: GSTM3 NM_000849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 19 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	NM_000849.5	MANE Select	c.580-123G>A		intron	N/A	NP_000840.2
	GSTM3	NR_024537.2		n.814-123G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.580-123G>A		intron	N/A	ENSP00000354357.2	P21266
	GSTM3	ENST00000256594.7	TSL:1	c.580-123G>A		intron	N/A	ENSP00000256594.3	P21266
	GSTM3	ENST00000872817.1		c.829-123G>A		intron	N/A	ENSP00000542876.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42268 AN: 152036 Hom.: 7062 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.338 AC: 224714 AN: 664836 Hom.: 42542 Cov.: 8 AF XY: 0.343 AC XY: 121588 AN XY: 354656

African (AFR) AF: 0.125 AC: 2302 AN: 18366

American (AMR) AF: 0.427 AC: 15017 AN: 35130

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 5237 AN: 19808

East Asian (EAS) AF: 0.744 AC: 26278 AN: 35306

South Asian (SAS) AF: 0.428 AC: 27905 AN: 65166

European-Finnish (FIN) AF: 0.299 AC: 15145 AN: 50588

Middle Eastern (MID) AF: 0.291 AC: 1218 AN: 4190

European-Non Finnish (NFE) AF: 0.300 AC: 120733 AN: 402262

Other (OTH) AF: 0.320 AC: 10879 AN: 34020

GnomAD4 genome AF: 0.278 AC: 42302 AN: 152154 Hom.: 7068 Cov.: 33 AF XY: 0.281 AC XY: 20889 AN XY: 74372

African (AFR) AF: 0.137 AC: 5683 AN: 41514

American (AMR) AF: 0.344 AC: 5253 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 932 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3790 AN: 5172

South Asian (SAS) AF: 0.423 AC: 2040 AN: 4828

European-Finnish (FIN) AF: 0.289 AC: 3055 AN: 10574

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20672 AN: 67982

Other (OTH) AF: 0.290 AC: 614 AN: 2114

Alfa AF: 0.299 Hom.: 15643

Bravo AF: 0.277

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.34
PhyloP100		-0.35
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: rs1571858; hg19: chr1-110279914; COSMIC: COSV56662075; COSMIC: COSV56662075;