chr1-109669533-C-G

Variant names:

• chr1-109669533-C-G
• rs1647455087
• NM_000848.4:c.322C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_000848.4(GSTM2):​c.322C>G​(p.Arg108Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,214 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GSTM2 NM_000848.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.970
• Publications: 0 publications found

Genes affected

GSTM2 (HGNC:4634): (glutathione S-transferase mu 2) 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. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000848.4. 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
	GSTM2	NM_000848.4	MANE Select	c.322C>G	p.Arg108Gly	missense	Exon 5 of 8	NP_000839.1	P28161-1
	GSTM2	NM_001142368.2		c.322C>G	p.Arg108Gly	missense	Exon 5 of 9	NP_001135840.1	P28161-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM2	ENST00000241337.9	TSL:1 MANE Select	c.322C>G	p.Arg108Gly	missense	Exon 5 of 8	ENSP00000241337.4	P28161-1
	GSTM2	ENST00000414179.6	TSL:1	c.10C>G	p.Arg4Gly	missense	Exon 5 of 9	ENSP00000404662.2	E9PGV1
	GSTM2	ENST00000864527.1		c.595C>G	p.Arg199Gly	missense	Exon 4 of 7	ENSP00000534586.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460214 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 726130

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26126

East Asian (EAS) AF: 0.00 AC: 0 AN: 39638

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110562

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.81
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.95
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.61	T
M_CAP	Benign	0.0070	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.4	M
PhyloP100		0.97
PROVEAN	Pathogenic	-4.8	D
REVEL	Benign	0.16
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.052	T
Polyphen		0.91	P
Vest4		0.70
MutPred		0.69		Gain of loop (P = 0.0502)
MVP		0.18
MPC		1.5
ClinPred		0.93	D
GERP RS		-1.4
Varity_R		0.77
gMVP		0.70
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs1647455087; hg19: chr1-110212155;