rs1109138

Variant names:

• chr1-109735327-T-C
• rs1109138
• NM_000849.5:c.*1744A>G

Your query was ambiguous. Multiple possible variants found:

• chr1-109735327-T-C
• chr1-109735327-T-A
• chr1-109735327-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000849.5(GSTM3):​c.*1744A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,994 control chromosomes in the GnomAD database, including 36,416 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.68 (36403 hom., cov: 31)
  • Exomes 𝑓: 0.67 (13 hom.)
• Consequence: GSTM3 NM_000849.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• Publications: 25 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000849.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	NM_000849.5	MANE Select	c.*1744A>G		3_prime_UTR	Exon 9 of 9	NP_000840.2
	GSTM3	NR_024537.2		n.2656A>G		non_coding_transcript_exon	Exon 8 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.*1744A>G		3_prime_UTR	Exon 9 of 9	ENSP00000354357.2	P21266
	GSTM3	ENST00000256594.7	TSL:1	c.*1744A>G		3_prime_UTR	Exon 8 of 8	ENSP00000256594.3	P21266
	GSTM5	ENST00000429410.2	TSL:2	n.82+22979T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103247 AN: 151816 Hom.: 36342 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.642

GnomAD4 exome AF: 0.667 AC: 40 AN: 60 Hom.: 13 Cov.: 0 AF XY: 0.674 AC XY: 31 AN XY: 46

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.750 AC: 3 AN: 4

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.659 AC: 29 AN: 44

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.680 AC: 103367 AN: 151934 Hom.: 36403 Cov.: 31 AF XY: 0.678 AC XY: 50358 AN XY: 74266

African (AFR) AF: 0.865 AC: 35877 AN: 41486

American (AMR) AF: 0.641 AC: 9787 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2051 AN: 3470

East Asian (EAS) AF: 0.845 AC: 4359 AN: 5156

South Asian (SAS) AF: 0.706 AC: 3389 AN: 4802

European-Finnish (FIN) AF: 0.556 AC: 5859 AN: 10534

Middle Eastern (MID) AF: 0.629 AC: 185 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39917 AN: 67914

Other (OTH) AF: 0.645 AC: 1355 AN: 2102

Alfa AF: 0.624 Hom.: 25591

Bravo AF: 0.692

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.96
DANN	Benign	0.44
PhyloP100		-1.3
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: rs1109138; hg19: chr1-110277949;