1-109715232-C-T

Position:

chr1-109715232-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_000851.4(GSTM5):c.559C>T(p.Arg187Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0069 in 1,614,192 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 9 hom., cov: 33)

Exomes 𝑓: 0.0070 ( 54 hom. )

Consequence

GSTM5
NM_000851.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.95

Variant links:

Genes affected

GSTM5 (HGNC:4637): (glutathione S-transferase mu 5) 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. Diversification of these genes has occurred in regions encoding substrate-binding domains, as well as in tissue expression patterns, to accommodate an increasing number of foreign compounds. [provided by RefSeq, Jul 2008]

GSTM5 links:

GSTM5 (HGNC:):

GSTM5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011373311).

BP6

Variant 1-109715232-C-T is Benign according to our data. Variant chr1-109715232-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 708302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM5	NM_000851.4 linkuse as main transcript	c.559C>T	p.Arg187Cys	missense_variant	7/8	ENST00000256593.8	NP_000842.2	P46439Q5T8R2
GSTM5	XM_005270784.5 linkuse as main transcript	c.559C>T	p.Arg187Cys	missense_variant	8/9		XP_005270841.1	P46439Q5T8R2
GSTM5	XM_005270785.5 linkuse as main transcript	c.247C>T	p.Arg83Cys	missense_variant	4/5		XP_005270842.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM5	ENST00000256593.8 linkuse as main transcript	c.559C>T	p.Arg187Cys	missense_variant	7/8	1	NM_000851.4	ENSP00000256593.3		P46439

Frequencies

GnomAD3 genomes

AF:

0.00548

AC:

834

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00596

Gnomad ASJ

AF:

0.00923

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00883

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00560

AC:

1409

AN:

251496

Hom.:

AF XY:

0.00566

AC XY:

769

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00494

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00134

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00868

Gnomad OTH exome

AF:

0.00863

GnomAD4 exome

AF:

0.00705

AC:

10301

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00686

AC XY:

4992

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000956

Gnomad4 AMR exome

AF:

0.00521

Gnomad4 ASJ exome

AF:

0.0115

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000916

Gnomad4 FIN exome

AF:

0.000768

Gnomad4 NFE exome

AF:

0.00815

Gnomad4 OTH exome

AF:

0.00778

GnomAD4 genome

AF:

0.00548

AC:

834

AN:

152304

Hom.:

Cov.:

AF XY:

0.00491

AC XY:

366

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00595

Gnomad4 ASJ

AF:

0.00923

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00883

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.00596

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00830

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00977

AC:

ExAC

AF:

0.00553

AC:

671

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.00927

EpiControl

AF:

0.0113

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2022	GSTM5: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 02, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

.;T;T

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.93

D;D;D

M_CAP

Pathogenic

0.29

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Pathogenic

4.0

.;H;.

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-5.8

.;D;D

REVEL

Benign

0.22

Sift

Benign

0.042

.;D;D

Sift4G

Uncertain

0.023

.;D;D

Polyphen

0.73

.;P;.

Vest4

0.76, 0.58

MVP

0.29

MPC

0.47

ClinPred

0.11

GERP RS

5.0

Varity_R

0.40

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over