rs6681

Variant names:

• chr1-165649842-C-A
• 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. Variant got 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. 14/18 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R13C) 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

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

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=0.08969885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGST3	NM_004528.4	c.-6C>A		splice_region_variant	Exon 2 of 6	ENST00000367889.8	NP_004519.1
MGST3	NM_004528.4	c.-6C>A		5_prime_UTR_variant	Exon 2 of 6	ENST00000367889.8	NP_004519.1
MGST3	XM_047421030.1	c.37C>A	p.Arg13Ser	missense_variant, splice_region_variant	Exon 3 of 7		XP_047276986.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGST3	ENST00000367889.8	c.-6C>A		splice_region_variant	Exon 2 of 6	1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367883.3	c.37C>A	p.Arg13Ser	missense_variant, splice_region_variant	Exon 3 of 7	3		ENSP00000356858.1
MGST3	ENST00000367885.5	c.37C>A	p.Arg13Ser	missense_variant, splice_region_variant	Exon 3 of 7	2		ENSP00000356860.1
MGST3	ENST00000367884.6	c.-6C>A		splice_region_variant	Exon 3 of 7	3		ENSP00000356859.1
MGST3	ENST00000367889	c.-6C>A		5_prime_UTR_variant	Exon 2 of 6	1	NM_004528.4	ENSP00000356864.3
MGST3	ENST00000367884	c.-6C>A		5_prime_UTR_variant	Exon 3 of 7	3		ENSP00000356859.1

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

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
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;T;T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	0.50	N;N;.
REVEL	Benign	0.066
Sift	Benign	0.066	T;T;.
Sift4G	Benign	0.54	T;T;T
Polyphen		0.0	B;B;B
Vest4		0.11
MutPred		0.29		Loss of helix (P = 0.0196);Loss of helix (P = 0.0196);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-165619079;