chr12-16363979-G-T

Variant names:

• chr12-16363979-G-T
• rs11555873
• NM_020300.5:c.406G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_020300.5(MGST1):​c.406G>T​(p.Val136Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
• Consequence: MGST1 NM_020300.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.20919287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST1	NM_020300.5	c.406G>T	p.Val136Phe	missense_variant	Exon 4 of 4	ENST00000396210.8	NP_064696.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST1	ENST00000396210.8	c.406G>T	p.Val136Phe	missense_variant	Exon 4 of 4	1	NM_020300.5	ENSP00000379513.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T;.;T;T;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.83	.;T;.;D;.
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.21	T;T;T;T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Uncertain	2.4	M;.;M;M;M
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.6	D;D;D;D;D
REVEL	Benign	0.29
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.12	T;T;T;T;T
Polyphen		0.10	B;.;B;B;B
Vest4		0.41
MutPred		0.47		Gain of helix (P = 0.132);.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.36
MPC		0.018
ClinPred		0.22	T
GERP RS		-2.1
Varity_R		0.13
gMVP		0.80

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: rs11555873; hg19: chr12-16516913;