Variant chr1-109690516-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000561.4(GSTM1):c.519G>C(p.Lys173Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K173R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.27 ( 9154 hom., cov: 11)

Exomes 𝑓: 0.38 ( 111272 hom. )

Consequence

GSTM1
NM_000561.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0570

Variant links:

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]

GSTM1 links:

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]

GSTM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.7616996E-6).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM1	NM_000561.4 link	c.519G>C	p.Lys173Asn	missense_variant	7/8	ENST00000309851.10	NP_000552.2	P09488-1X5DR03
GSTM1	XM_005270782.6 link	c.417G>C	p.Lys139Asn	missense_variant	7/8		XP_005270839.1
GSTM1	NM_146421.3 link	c.456+150G>C		intron_variant			NP_666533.1	P09488-2X5D932

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM1	ENST00000309851.10 link	c.519G>C	p.Lys173Asn	missense_variant	7/8	1	NM_000561.4	ENSP00000311469.5		P09488-1

Frequencies

GnomAD3 genomes

AF:

0.268

AC:

21474

AN:

80058

Hom.:

9146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.0785

Gnomad AMR

AF:

0.350

Gnomad ASJ

AF:

0.392

Gnomad EAS

AF:

0.647

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.300

Gnomad NFE

AF:

0.349

Gnomad OTH

AF:

0.304

GnomAD3 exomes

AF:

0.362

AC:

52343

AN:

144724

Hom.:

21395

AF XY:

0.356

AC XY:

27753

AN XY:

77924

show subpopulations

Gnomad AFR exome

AF:

0.0981

Gnomad AMR exome

AF:

0.474

Gnomad ASJ exome

AF:

0.368

Gnomad EAS exome

AF:

0.645

Gnomad SAS exome

AF:

0.219

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.368

Gnomad OTH exome

AF:

0.365

GnomAD4 exome

AF:

0.384

AC:

265781

AN:

692526

Hom.:

111272

Cov.:

AF XY:

0.378

AC XY:

132236

AN XY:

349856

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.477

Gnomad4 ASJ exome

AF:

0.398

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.229

Gnomad4 FIN exome

AF:

0.462

Gnomad4 NFE exome

AF:

0.393

Gnomad4 OTH exome

AF:

0.353

GnomAD4 genome

AF:

0.268

AC:

21499

AN:

80176

Hom.:

9154

Cov.:

AF XY:

0.270

AC XY:

10495

AN XY:

38888

show subpopulations

Gnomad4 AFR

AF:

0.101

Gnomad4 AMR

AF:

0.351

Gnomad4 ASJ

AF:

0.392

Gnomad4 EAS

AF:

0.649

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.349

Gnomad4 OTH

AF:

0.303

Alfa

AF:

0.328

Hom.:

803

ESP6500AA

AF:

0.119

AC:

495

ESP6500EA

AF:

0.396

AC:

2632

ExAC

AF:

0.468

AC:

50024

Asia WGS

AF:

0.352

AC:

689

AN:

1964

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.061

T;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.25

T;T

MetaRNN

Benign

0.0000038

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.074

Sift

Benign

0.15

T;T

Sift4G

Benign

0.31

T;T

Polyphen

0.028

B;.

Vest4

0.082

MutPred

0.11

Loss of methylation at K173 (P = 0.0027);.;

MPC

1.2

ClinPred

0.010

GERP RS

-1.1

Varity_R

0.33

gMVP

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over