1-109740350-G-T

Position:

• chr1-109740350-G-T

Variant summary

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

The NM_000849.5(GSTM3):​c.-63C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 1,456,204 control chromosomes in the GnomAD database, including 267,128 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 0.66 (34123 hom., cov: 33)
  • Exomes 𝑓: 0.59 (233005 hom.)
• Consequence: GSTM3 NM_000849.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907

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=-0.67).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM3	NM_000849.5	c.-63C>A		5_prime_UTR_variant	2/9	ENST00000361066.7
GSTM3	NR_024537.2	n.248C>A		non_coding_transcript_exon_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM3	ENST00000361066.7	c.-63C>A		5_prime_UTR_variant	2/9	1	NM_000849.5	P1
	ENST00000431955.1	n.627+3209G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100187 AN: 151988 Hom.: 34076 Cov.: 33

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.843

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.572

Gnomad OTH AF: 0.620

GnomAD3 exomes AF: 0.635 AC: 132193 AN: 208154 Hom.: 42586 AF XY: 0.631 AC XY: 71158 AN XY: 112822

Gnomad AFR exome AF: 0.837

Gnomad AMR exome AF: 0.664

Gnomad ASJ exome AF: 0.535

Gnomad EAS exome AF: 0.849

Gnomad SAS exome AF: 0.702

Gnomad FIN exome AF: 0.549

Gnomad NFE exome AF: 0.571

Gnomad OTH exome AF: 0.583

GnomAD4 exome AF: 0.594 AC: 774086 AN: 1304100 Hom.: 233005 Cov.: 18 AF XY: 0.596 AC XY: 389601 AN XY: 653982

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.659

Gnomad4 ASJ exome AF: 0.534

Gnomad4 EAS exome AF: 0.832

Gnomad4 SAS exome AF: 0.694

Gnomad4 FIN exome AF: 0.548

Gnomad4 NFE exome AF: 0.569

Gnomad4 OTH exome AF: 0.607

GnomAD4 genome AF: 0.659 AC: 100290 AN: 152104 Hom.: 34123 Cov.: 33 AF XY: 0.659 AC XY: 48971 AN XY: 74350

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.572

Gnomad4 OTH AF: 0.623

Alfa AF: 0.606 Hom.: 11363

Bravo AF: 0.670

Asia WGS AF: 0.741 AC: 2581 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.1
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1332018; hg19: chr1-110282972;