Genetic Variant NM_000850.5:c.534T>C (chr1-109659077-T-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_000850.5(GSTM4):c.534T>C(p.Phe178Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.86 in 1,614,000 control chromosomes in the GnomAD database, including 599,512 homozygotes. 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 0.80 ( 50007 hom., cov: 32)

Exomes 𝑓: 0.87 ( 549505 hom. )

Consequence

GSTM4
NM_000850.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.181

Variant links:

Genes affected

GSTM4 (HGNC:4636): (glutathione S-transferase mu 4) 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. Multiple transcript variants, each encoding a distinct protein isoform, have been identified. [provided by RefSeq, Jul 2008]

GSTM4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP7

Synonymous conserved (PhyloP=0.181 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.95 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSTM4	NM_000850.5 link	c.534T>C	p.Phe178Phe	synonymous_variant	Exon 7 of 8	ENST00000369836.9	NP_000841.1	Q03013-1A0A140VKE3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSTM4	ENST00000369836.9 link	c.534T>C	p.Phe178Phe	synonymous_variant	Exon 7 of 8	1	NM_000850.5	ENSP00000358851.4		Q03013-1

Frequencies

GnomAD3 genomes

AF:

0.801

AC:

121815

AN:

152020

Hom.:

49990

Cov.:

show subpopulations

Gnomad AFR

AF:

0.603

Gnomad AMI

AF:

0.828

Gnomad AMR

AF:

0.869

Gnomad ASJ

AF:

0.862

Gnomad EAS

AF:

0.972

Gnomad SAS

AF:

0.872

Gnomad FIN

AF:

0.891

Gnomad MID

AF:

0.804

Gnomad NFE

AF:

0.870

Gnomad OTH

AF:

0.822

GnomAD3 exomes

AF:

0.868

AC:

218229

AN:

251494

Hom.:

95437

AF XY:

0.871

AC XY:

118342

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.593

Gnomad AMR exome

AF:

0.921

Gnomad ASJ exome

AF:

0.858

Gnomad EAS exome

AF:

0.978

Gnomad SAS exome

AF:

0.873

Gnomad FIN exome

AF:

0.885

Gnomad NFE exome

AF:

0.869

Gnomad OTH exome

AF:

0.869

GnomAD4 exome

AF:

0.866

AC:

1265423

AN:

1461862

Hom.:

549505

Cov.:

AF XY:

0.866

AC XY:

629959

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.583

Gnomad4 AMR exome

AF:

0.915

Gnomad4 ASJ exome

AF:

0.857

Gnomad4 EAS exome

AF:

0.967

Gnomad4 SAS exome

AF:

0.873

Gnomad4 FIN exome

AF:

0.890

Gnomad4 NFE exome

AF:

0.868

Gnomad4 OTH exome

AF:

0.857

GnomAD4 genome

AF:

0.801

AC:

121868

AN:

152138

Hom.:

50007

Cov.:

AF XY:

0.805

AC XY:

59886

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.603

Gnomad4 AMR

AF:

0.870

Gnomad4 ASJ

AF:

0.862

Gnomad4 EAS

AF:

0.972

Gnomad4 SAS

AF:

0.872

Gnomad4 FIN

AF:

0.891

Gnomad4 NFE

AF:

0.870

Gnomad4 OTH

AF:

0.823

Alfa

AF:

0.829

Hom.:

12064

Bravo

AF:

0.792

Asia WGS

AF:

0.894

AC:

3107

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.2

DANN

Benign

0.46

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over