1-165649842-C-G

Variant names:

• chr1-165649842-C-G
• rs6681
• NM_004528.4:c.-6C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000367885.5(MGST3):​c.37C>G​(p.Arg13Gly) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,124 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/19 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: MGST3 ENST00000367885.5 missense, splice_region
• Scores: Splicing: ADA: 0.00002666
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 13 publications found

Genes affected

MGST3 (HGNC:7064): (microsomal glutathione S-transferase 3) This gene encodes a member of the MAPEG (Membrane Associated Proteins in Eicosanoid and Glutathione metabolism) protein family. Members of this family are involved in the production of leukotrienes and prostaglandin E, important mediators of inflammation. This gene encodes an enzyme which catalyzes the conjugation of leukotriene A4 and reduced glutathione to produce leukotriene C4. This enzyme also demonstrates glutathione-dependent peroxidase activity towards lipid hydroperoxides.[provided by RefSeq, May 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07980612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000367885.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	NM_004528.4	MANE Select	c.-6C>G		splice_region	Exon 2 of 6	NP_004519.1	O14880
	MGST3	NM_004528.4	MANE Select	c.-6C>G		5_prime_UTR	Exon 2 of 6	NP_004519.1	O14880

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGST3	ENST00000367889.8	TSL:1 MANE Select	c.-6C>G		splice_region	Exon 2 of 6	ENSP00000356864.3	O14880
	MGST3	ENST00000367883.3	TSL:3	c.37C>G	p.Arg13Gly	missense splice_region	Exon 3 of 7	ENSP00000356858.1	Q5VV89
	MGST3	ENST00000367885.5	TSL:2	c.37C>G	p.Arg13Gly	missense splice_region	Exon 3 of 7	ENSP00000356860.1	Q5VV89

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152124 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74316

African (AFR) AF: 0.0000483 AC: 2 AN: 41434

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68026

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 493

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	2.9
DANN	Benign	0.42
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.0014	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.080	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.50
PROVEAN	Benign	0.51	N
REVEL	Benign	0.058
Sift	Benign	0.057	T
Sift4G	Benign	0.57	T
Polyphen		0.0	B
Vest4		0.085
MutPred		0.32		Gain of sheet (P = 0.0043)
MVP		0.50
ClinPred		0.033	T
GERP RS		1.3
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000027
dbscSNV1_RF	Benign	0.0040
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

Other links and lift over

dbSNP: rs6681; hg19: chr1-165619079;