rs12068997

Variant names:

• chr1-109688214-C-A
• rs12068997
• NM_000561.4:c.81C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-109688214-C-A
• chr1-109688214-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_000561.4(GSTM1):​c.81C>A​(p.Ser27Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict 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: 0.0000028 (1 hom.)
• Consequence: GSTM1 NM_000561.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.544
• Publications: 6 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19664624).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM1	NM_000561.4	c.81C>A	p.Ser27Arg	missense_variant	Exon 2 of 8	ENST00000309851.10	NP_000552.2
GSTM1	NM_146421.3	c.81C>A	p.Ser27Arg	missense_variant	Exon 2 of 7		NP_666533.1
GSTM1	XM_005270782.6	c.-22C>A		5_prime_UTR_variant	Exon 2 of 8		XP_005270839.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10	c.81C>A	p.Ser27Arg	missense_variant	Exon 2 of 8	1	NM_000561.4	ENSP00000311469.5

Frequencies

GnomAD3 genomes Cov.: 13

GnomAD2 exomes AF: 0.0000151 AC: 2 AN: 132316 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: 0.000641

GnomAD4 exome AF: 0.00000280 AC: 2 AN: 715530 Hom.: 1 Cov.: 4 AF XY: 0.00 AC XY: 0 AN XY: 357470

African (AFR) AF: 0.00 AC: 0 AN: 24528

American (AMR) AF: 0.00 AC: 0 AN: 25042

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 51910

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28932

Middle Eastern (MID) AF: 0.000781 AC: 2 AN: 2560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 521146

Other (OTH) AF: 0.00 AC: 0 AN: 29998

GnomAD4 genome Cov.: 13

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.085	T;T;.;.;.
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.65
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.82	T;T;T;D;T
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.20	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M;.;M;.;.
PhyloP100		0.54
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-2.0	N;N;N;D;N
REVEL	Benign	0.042
Sift	Benign	0.18	T;T;T;T;T
Sift4G	Benign	0.21	T;T;T;T;T
Polyphen		0.98	D;.;B;.;.
Vest4		0.20
MutPred		0.34		Loss of ubiquitination at K32 (P = 0.0383);Loss of ubiquitination at K32 (P = 0.0383);Loss of ubiquitination at K32 (P = 0.0383);Loss of ubiquitination at K32 (P = 0.0383);Loss of ubiquitination at K32 (P = 0.0383);
MVP		0.20
MPC		1.2
ClinPred		0.18	T
GERP RS		1.5
PromoterAI		0.0081	Neutral
Varity_R		0.16
gMVP		0.53
Mutation Taster		=90/10	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: rs12068997; hg19: chr1-110230836;