1-109735327-T-C

Position:

• chr1-109735327-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000849.5(GSTM3):​c.*1744A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 151,994 control chromosomes in the GnomAD database, including 36,416 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 0.68 (36403 hom., cov: 31)
  • Exomes 𝑓: 0.67 (13 hom.)
• Consequence: GSTM3 NM_000849.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25

Genes affected

GSTM3 (HGNC:4635): (glutathione S-transferase mu 3) 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. Mutations of this class mu gene have been linked with a slight increase in a number of cancers, likely due to exposure with environmental toxins. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]

GSTM3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSTM3	NM_000849.5	c.*1744A>G		3_prime_UTR_variant	9/9	ENST00000361066.7	NP_000840.2
GSTM3	NR_024537.2	n.2656A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSTM3	ENST00000361066.7	c.*1744A>G		3_prime_UTR_variant	9/9	1	NM_000849.5	ENSP00000354357.2
GSTM3	ENST00000256594.7	c.*1744A>G		3_prime_UTR_variant	8/8	1		ENSP00000256594.3
GSTM5	ENST00000429410.2	n.82+22979T>C		intron_variant		2
ENSG00000241720	ENST00000431955.1	n.426-1613T>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.680 AC: 103247 AN: 151816 Hom.: 36342 Cov.: 31

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.645

Gnomad AMR AF: 0.641

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.706

Gnomad FIN AF: 0.556

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.642

GnomAD4 exome AF: 0.667 AC: 40 AN: 60 Hom.: 13 Cov.: 0 AF XY: 0.674 AC XY: 31 AN XY: 46

Gnomad4 AFR exome AF: 0.750

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.659

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.680 AC: 103367 AN: 151934 Hom.: 36403 Cov.: 31 AF XY: 0.678 AC XY: 50358 AN XY: 74266

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.641

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.845

Gnomad4 SAS AF: 0.706

Gnomad4 FIN AF: 0.556

Gnomad4 NFE AF: 0.588

Gnomad4 OTH AF: 0.645

Alfa AF: 0.613 Hom.: 16801

Bravo AF: 0.692

Asia WGS AF: 0.749 AC: 2607 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.96
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs1109138; hg19: chr1-110277949;