rs3814309

Variant names:

• chr1-109734781-T-C
• rs3814309
• NM_000849.5:c.*2290A>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.*2290A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,286 control chromosomes in the GnomAD database, including 7,087 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 0.27 (7081 hom., cov: 32)
  • Exomes 𝑓: 0.28 (6 hom.)
• Consequence: GSTM3 NM_000849.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 25 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.*2290A>G		3_prime_UTR_variant	Exon 9 of 9	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.3202A>G		non_coding_transcript_exon_variant	Exon 8 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7	c.*2290A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_000849.5	ENSP00000354357.2
GSTM3	ENST00000256594.7	c.*2290A>G		3_prime_UTR_variant	Exon 8 of 8	1		ENSP00000256594.3
GSTM5	ENST00000429410.2	n.82+22433T>C		intron_variant	Intron 1 of 1	2
ENSG00000241720	ENST00000431955.1	n.426-2159T>C		intron_variant	Intron 2 of 3	3

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41461 AN: 152068 Hom.: 7075 Cov.: 32

Gnomad AFR AF: 0.106

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.342

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.280 AC: 28 AN: 100 Hom.: 6 Cov.: 0 AF XY: 0.269 AC XY: 21 AN XY: 78

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.267 AC: 23 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.273 AC: 41493 AN: 152186 Hom.: 7081 Cov.: 32 AF XY: 0.275 AC XY: 20479 AN XY: 74394

African (AFR) AF: 0.106 AC: 4420 AN: 41542

American (AMR) AF: 0.342 AC: 5233 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1121 AN: 3470

East Asian (EAS) AF: 0.747 AC: 3854 AN: 5158

South Asian (SAS) AF: 0.430 AC: 2077 AN: 4826

European-Finnish (FIN) AF: 0.289 AC: 3062 AN: 10588

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20866 AN: 67988

Other (OTH) AF: 0.289 AC: 610 AN: 2114

Alfa AF: 0.295 Hom.: 11557

Bravo AF: 0.270

Asia WGS AF: 0.510 AC: 1773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.86
PhyloP100		-0.069
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: rs3814309; hg19: chr1-110277403; COSMIC: COSV56661884; COSMIC: COSV56661884;