1-109737292-C-T

Position:

• chr1-109737292-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000849.5(GSTM3):​c.580-123G>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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.580-123G>A		intron_variant		ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.814-123G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7	c.580-123G>A		intron_variant		1	NM_000849.5	ENSP00000354357	P1
	ENST00000431955.1	n.627+151C>T		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.427

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.744

Gnomad4 SAS exome AF: 0.428

Gnomad4 FIN exome AF: 0.299

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.320

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

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.733

Gnomad4 SAS AF: 0.423

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.290

Alfa AF: 0.306 Hom.: 5008

Bravo AF: 0.277

Asia WGS AF: 0.502 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.34

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: rs1571858; hg19: chr1-110279914; COSMIC: COSV56662075; COSMIC: COSV56662075;