19-13768642-GG-AA

Variant names:

• chr19-13768642-GG-AA
• NM_001031727.4:c.629_630delGGinsAA
• MRI1 p.Arg210Gln

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001031727.4(MRI1):​c.629_630delGGinsAA​(p.Arg210Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R210W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MRI1 NM_001031727.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.94
• Publications: 0 publications found

Genes affected

MRI1 (HGNC:28469): (methylthioribose-1-phosphate isomerase 1) This enzyme functions in the methionine salvage pathway by catalyzing the interconversion of methylthioribose-1-phosphate and methythioribulose-1-phosphate. Elevated expression of the encoded protein is associated with metastatic melanoma and this protein promotes melanoma cell invasion independent of its enzymatic activity. Mutations in this gene may be associated with vanishing white matter disease (VMWD). [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031727.4. 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
	MRI1	NM_001031727.4	MANE Select	c.629_630delGGinsAA	p.Arg210Gln	missense	N/A	NP_001026897.1	Q9BV20-1
	MRI1	NM_001329572.2		c.542_543delGGinsAA	p.Arg181Gln	missense	N/A	NP_001316501.1
	MRI1	NM_032285.4		c.488_489delGGinsAA	p.Arg163Gln	missense	N/A	NP_115661.1	Q9BV20-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MRI1	ENST00000040663.8	TSL:1 MANE Select	c.629_630delGGinsAA	p.Arg210Gln	missense	N/A	ENSP00000040663.5	Q9BV20-1
	MRI1	ENST00000319545.12	TSL:1	c.488_489delGGinsAA	p.Arg163Gln	missense	N/A	ENSP00000314871.7	Q9BV20-2
	MRI1	ENST00000912602.1		c.644_645delGGinsAA	p.Arg215Gln	missense	N/A	ENSP00000582661.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		8.9

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-13879456;