NM_000561.4:c.45C>T

Variant names:

• chr1-109688178-C-T
• rs567320393
• NM_000561.4:c.45C>T

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_000561.4(GSTM1):​c.45C>T​(p.His15His) 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: not found (cov: 13)
  • Exomes 𝑓: 0.000066 (17 hom.)
• Consequence: GSTM1 NM_000561.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.388
• Publications: 1 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: Benign. The variant received -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP7: Synonymous conserved (PhyloP=-0.388 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 17 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	NM_000561.4	MANE Select	c.45C>T	p.His15His	synonymous	Exon 2 of 8	NP_000552.2
	GSTM1	NM_146421.3		c.45C>T	p.His15His	synonymous	Exon 2 of 7	NP_666533.1	X5D932

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GSTM1	ENST00000309851.10	TSL:1 MANE Select	c.45C>T	p.His15His	synonymous	Exon 2 of 8	ENSP00000311469.5	P09488-1
	GSTM1	ENST00000349334.7	TSL:1	c.45C>T	p.His15His	synonymous	Exon 2 of 7	ENSP00000234981.4	P09488-2
	GSTM1	ENST00000369819.2	TSL:1	c.45C>T	p.His15His	synonymous	Exon 2 of 6	ENSP00000358834.2	B9ZVX7

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD2 exomes AF: 0.0000906 AC: 12 AN: 132486 AF XY: 0.0000843

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 AF: 0.0000657 AC: 47 AN: 715552 Hom.: 17 Cov.: 0 AF XY: 0.000101 AC XY: 36 AN XY: 357502

African (AFR) AF: 0.0000815 AC: 2 AN: 24528

American (AMR) AF: 0.00 AC: 0 AN: 25060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13410

East Asian (EAS) AF: 0.00 AC: 0 AN: 18004

South Asian (SAS) AF: 0.000771 AC: 40 AN: 51910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28946

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2548

European-Non Finnish (NFE) AF: 0.00000384 AC: 2 AN: 521160

Other (OTH) AF: 0.000100 AC: 3 AN: 29986

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	8.9
DANN	Benign	0.92
PhyloP100		-0.39
PromoterAI		0.0019	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs567320393; hg19: chr1-110230800;