12-16363932-C-T

Position:

• chr12-16363932-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020300.5(MGST1):​c.359C>T​(p.Ala120Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MGST1 NM_020300.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.07

Genes affected

MGST1 (HGNC:7061): (microsomal glutathione S-transferase 1) The MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) family consists of six human proteins, two of which are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. Other family members, demonstrating glutathione S-transferase and peroxidase activities, are involved in cellular defense against toxic, carcinogenic, and pharmacologically active electrophilic compounds. This gene encodes a protein that catalyzes the conjugation of glutathione to electrophiles and the reduction of lipid hydroperoxides. This protein is localized to the endoplasmic reticulum and outer mitochondrial membrane where it is thought to protect these membranes from oxidative stress. Several transcript variants, some non-protein coding and some protein coding, have been found for this gene. [provided by RefSeq, May 2012]

MGST1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MGST1	NM_020300.5	c.359C>T	p.Ala120Val	missense_variant	4/4	ENST00000396210.8	NP_064696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000396210.8	c.359C>T	p.Ala120Val	missense_variant	4/4	1	NM_020300.5	ENSP00000379513.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2024

The c.359C>T (p.A120V) alteration is located in exon 4 (coding exon 3) of the MGST1 gene. This alteration results from a C to T substitution at nucleotide position 359, causing the alanine (A) at amino acid position 120 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.12	T;.;T;T;T
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.076
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.93	.;D;.;D;.
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.60	D;D;D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.4	L;.;L;L;L
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.7	D;N;D;D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0080	D;T;D;D;D
Sift4G	Benign	0.15	T;T;T;T;T
Polyphen		0.93	P;.;P;P;P
Vest4		0.41
MutPred		0.68		Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);
MVP		0.51
MPC		0.018
ClinPred		0.65	D
GERP RS		5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.60

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: rs1940115328; hg19: chr12-16516866;