1-109739319-G-A

Position:

• chr1-109739319-G-A

Variant summary

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

The NM_000849.5(GSTM3):​c.189+110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.631 in 630,142 control chromosomes in the GnomAD database, including 128,823 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 0.67 (35490 hom., cov: 31)
  • Exomes 𝑓: 0.62 (93333 hom.)
• Consequence: GSTM3 NM_000849.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GSTM3	NM_000849.5	c.189+110C>T		intron_variant		ENST00000361066.7
GSTM3	NR_024537.2	n.423+110C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSTM3	ENST00000361066.7	c.189+110C>T		intron_variant		1	NM_000849.5	P1
	ENST00000431955.1	n.627+2178G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.671 AC: 101996 AN: 151918 Hom.: 35435 Cov.: 31

Gnomad AFR AF: 0.851

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.632

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.700

Gnomad FIN AF: 0.557

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.618 AC: 295297 AN: 478106 Hom.: 93333 AF XY: 0.617 AC XY: 155594 AN XY: 252210

Gnomad4 AFR exome AF: 0.851

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.542

Gnomad4 EAS exome AF: 0.830

Gnomad4 SAS exome AF: 0.696

Gnomad4 FIN exome AF: 0.551

Gnomad4 NFE exome AF: 0.580

Gnomad4 OTH exome AF: 0.621

GnomAD4 genome AF: 0.672 AC: 102109 AN: 152036 Hom.: 35490 Cov.: 31 AF XY: 0.670 AC XY: 49818 AN XY: 74300

Gnomad4 AFR AF: 0.851

Gnomad4 AMR AF: 0.632

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.841

Gnomad4 SAS AF: 0.700

Gnomad4 FIN AF: 0.557

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.630

Alfa AF: 0.595 Hom.: 35876

Bravo AF: 0.682

Asia WGS AF: 0.743 AC: 2588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.65

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: rs10735234; hg19: chr1-110281941;