chr1-109690516-G-A

Variant names:

• chr1-109690516-G-A
• rs1065411
• NM_000561.4:c.519G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_000561.4(GSTM1):​c.519G>A​(p.Lys173Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0000028 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSTM1 NM_000561.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 51 publications found

Genes affected

GSTM1 (HGNC:4632): (glutathione S-transferase mu 1) 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. Null mutations of this class mu gene have been linked with an increase in a number of cancers, likely due to an increased susceptibility to environmental toxins and carcinogens. Multiple protein isoforms are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.057 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000561.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	NM_000561.4	MANE Select	c.519G>A	p.Lys173Lys	synonymous	Exon 7 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.456+150G>A		intron	N/A	NP_666533.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	ENST00000309851.10	TSL:1 MANE Select	c.519G>A	p.Lys173Lys	synonymous	Exon 7 of 8	ENSP00000311469.5
	GSTM1	ENST00000349334.7	TSL:1	c.456+150G>A		intron	N/A	ENSP00000234981.4
	GSTM1	ENST00000369819.2	TSL:1	c.360+1191G>A		intron	N/A	ENSP00000358834.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 80070 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.00

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

GnomAD2 exomes AF: 0.00 AC: 0 AN: 144724 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000280 AC: 2 AN: 713702 Hom.: 1 Cov.: 14 AF XY: 0.00000555 AC XY: 2 AN XY: 360058

African (AFR) AF: 0.00 AC: 0 AN: 25306

American (AMR) AF: 0.00 AC: 0 AN: 27602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14294

East Asian (EAS) AF: 0.00 AC: 0 AN: 19166

South Asian (SAS) AF: 0.00 AC: 0 AN: 52190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2642

European-Non Finnish (NFE) AF: 0.00000391 AC: 2 AN: 511800

Other (OTH) AF: 0.00 AC: 0 AN: 30102

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 80070 Hom.: 0 Cov.: 11 AF XY: 0.00 AC XY: 0 AN XY: 38774

African (AFR) AF: 0.00 AC: 0 AN: 28252

American (AMR) AF: 0.00 AC: 0 AN: 7490

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1752

East Asian (EAS) AF: 0.00 AC: 0 AN: 2124

South Asian (SAS) AF: 0.00 AC: 0 AN: 2668

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5154

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 140

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31116

Other (OTH) AF: 0.00 AC: 0 AN: 1030

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.82
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1065411; hg19: chr1-110233138;