1-109736350-C-T

Position:

• chr1-109736350-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.*721G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.549 in 151,874 control chromosomes in the GnomAD database, including 23,341 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 0.55 (23341 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: GSTM3 NM_000849.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.679

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.822 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.*721G>A		3_prime_UTR_variant	9/9	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.1633G>A		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066	c.*721G>A		3_prime_UTR_variant	9/9	1	NM_000849.5	ENSP00000354357.2
GSTM3	ENST00000256594	c.*721G>A		3_prime_UTR_variant	8/8	1		ENSP00000256594.3
GSTM5	ENST00000429410.2	n.82+24002C>T		intron_variant		2
ENSG00000241720	ENST00000431955.1	n.426-590C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.549 AC: 83245 AN: 151758 Hom.: 23313 Cov.: 32

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.562

Gnomad ASJ AF: 0.445

Gnomad EAS AF: 0.844

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.523

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.549 AC: 83326 AN: 151874 Hom.: 23341 Cov.: 32 AF XY: 0.549 AC XY: 40723 AN XY: 74218

Gnomad4 AFR AF: 0.595

Gnomad4 AMR AF: 0.563

Gnomad4 ASJ AF: 0.445

Gnomad4 EAS AF: 0.843

Gnomad4 SAS AF: 0.607

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.527

Alfa AF: 0.506 Hom.: 12605

Bravo AF: 0.555

Asia WGS AF: 0.679 AC: 2355 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.41

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: rs1537236; hg19: chr1-110278972;