chr1-109712552-T-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000851.4(GSTM5):​c.37-66T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,418,824 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 32)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

GSTM5
NM_000851.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.578

Publications

25 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSTM5NM_000851.4 linkc.37-66T>C intron_variant Intron 1 of 7 ENST00000256593.8 NP_000842.2 P46439Q5T8R2
GSTM5XM_005270784.5 linkc.37-66T>C intron_variant Intron 2 of 8 XP_005270841.1 P46439Q5T8R2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GSTM5ENST00000256593.8 linkc.37-66T>C intron_variant Intron 1 of 7 1 NM_000851.4 ENSP00000256593.3 P46439

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.05e-7
AC:
1
AN:
1418824
Hom.:
0
Cov.:
28
AF XY:
0.00000141
AC XY:
1
AN XY:
708476
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
32630
American (AMR)
AF:
0.00
AC:
0
AN:
44660
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25856
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39482
South Asian (SAS)
AF:
0.0000117
AC:
1
AN:
85388
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53258
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5374
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1073324
Other (OTH)
AF:
0.00
AC:
0
AN:
58852
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.1
DANN
Benign
0.33
PhyloP100
-0.58
PromoterAI
0.086
Neutral

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

Publications

Other links and lift over

dbSNP: rs929166; hg19: chr1-110255174; API