chr1-109739319-G-A

Variant names:

• chr1-109739319-G-A
• rs10735234
• NM_000849.5:c.189+110C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 44 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=-0.96).
• 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 rank	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.189+110C>T		intron_variant	Intron 4 of 8	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.423+110C>T		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7	c.189+110C>T		intron_variant	Intron 4 of 8	1	NM_000849.5	ENSP00000354357.2

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

African (AFR) AF: 0.851 AC: 12520 AN: 14706

American (AMR) AF: 0.660 AC: 18906 AN: 28654

Ashkenazi Jewish (ASJ) AF: 0.542 AC: 7082 AN: 13056

East Asian (EAS) AF: 0.830 AC: 28843 AN: 34756

South Asian (SAS) AF: 0.696 AC: 22911 AN: 32940

European-Finnish (FIN) AF: 0.551 AC: 23510 AN: 42676

Middle Eastern (MID) AF: 0.589 AC: 1744 AN: 2962

European-Non Finnish (NFE) AF: 0.580 AC: 164169 AN: 283214

Other (OTH) AF: 0.621 AC: 15612 AN: 25142

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

African (AFR) AF: 0.851 AC: 35328 AN: 41506

American (AMR) AF: 0.632 AC: 9669 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.538 AC: 1867 AN: 3468

East Asian (EAS) AF: 0.841 AC: 4354 AN: 5176

South Asian (SAS) AF: 0.700 AC: 3365 AN: 4810

European-Finnish (FIN) AF: 0.557 AC: 5859 AN: 10522

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.582 AC: 39572 AN: 67950

Other (OTH) AF: 0.630 AC: 1334 AN: 2116

Alfa AF: 0.623 Hom.: 62630

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
PhyloP100		-0.37
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: rs10735234; hg19: chr1-110281941;