rs6681

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-165649842-C-A
• chr1-165649842-C-G
• chr1-165649842-C-T

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>A​(p.Arg13Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. 2/3 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. R13G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MGST3 ENST00000367885.5 missense, splice_region
• Scores: Splicing: ADA: 0.00002810
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.499
• Publications: 0 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=0.08969885).

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>A		splice_region	Exon 2 of 6	NP_004519.1	O14880
	MGST3	NM_004528.4	MANE Select	c.-6C>A		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>A		splice_region	Exon 2 of 6	ENSP00000356864.3	O14880
	MGST3	ENST00000367883.3	TSL:3	c.37C>A	p.Arg13Ser	missense splice_region	Exon 3 of 7	ENSP00000356858.1	Q5VV89
	MGST3	ENST00000367885.5	TSL:2	c.37C>A	p.Arg13Ser	missense splice_region	Exon 3 of 7	ENSP00000356860.1	Q5VV89

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461708 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727152

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5672

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111964

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.4
DANN	Benign	0.71
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.090	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.50
PROVEAN	Benign	0.50	N
REVEL	Benign	0.066
Sift	Benign	0.066	T
Sift4G	Benign	0.54	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.29		Loss of helix (P = 0.0196)
MVP		0.46
ClinPred		0.050	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=297/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000028
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 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;