1-109740350-G-A

Variant names:

• chr1-109740350-G-A
• rs1332018
• NM_000849.5:c.-63C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000849.5(GSTM3):​c.-63C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,022 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTM3 NM_000849.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.907
• Publications: 73 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

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.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	NP_000840.2
	GSTM3	NM_000849.5	MANE Select	c.-63C>T		5_prime_UTR	Exon 2 of 9	NP_000840.2
	GSTM3	NR_024537.2		n.248C>T		non_coding_transcript_exon	Exon 2 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 9	ENSP00000354357.2	P21266
	GSTM3	ENST00000256594.7	TSL:1	c.-63C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000256594.3	P21266
	GSTM3	ENST00000361066.7	TSL:1 MANE Select	c.-63C>T		5_prime_UTR	Exon 2 of 9	ENSP00000354357.2	P21266

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1306774 Hom.: 0 Cov.: 18 AF XY: 0.00 AC XY: 0 AN XY: 655202

African (AFR) AF: 0.00 AC: 0 AN: 29810

American (AMR) AF: 0.00 AC: 0 AN: 40346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24492

East Asian (EAS) AF: 0.00 AC: 0 AN: 37882

South Asian (SAS) AF: 0.00 AC: 0 AN: 80916

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51316

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5452

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 981480

Other (OTH) AF: 0.00 AC: 0 AN: 55080

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152022 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74242

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67978

Other (OTH) AF: 0.00 AC: 0 AN: 2092

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.1
DANN	Benign	0.94
PhyloP100		-0.91
PromoterAI		-0.068	Neutral

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: rs1332018; hg19: chr1-110282972;