19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A

Position:

• chr19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001031727.4(MRI1):​c.132+48_133-64del variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 1,238,100 control chromosomes in the GnomAD database, including 59,569 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (12582 hom., cov: 0)
  • Exomes 𝑓: 0.11 (46987 hom.)
• Consequence: MRI1 NM_001031727.4 splice_donor_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.31

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

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A is Benign according to our data. Variant chr19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1995432.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRI1	NM_001031727.4	c.132+48_133-64del		splice_donor_region_variant, intron_variant		ENST00000040663.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MRI1	ENST00000040663.8	c.132+48_133-64del		splice_donor_region_variant, intron_variant		1	NM_001031727.4	P1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 54699 AN: 112706 Hom.: 12575 Cov.: 0

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.661

Gnomad AMR AF: 0.478

Gnomad ASJ AF: 0.502

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.607

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.473

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.478

GnomAD3 exomes AF: 0.000108 AC: 9 AN: 83100 Hom.: 4 AF XY: 0.000142 AC XY: 7 AN XY: 49186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000698

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000771

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.109 AC: 122516 AN: 1125314 Hom.: 46987 AF XY: 0.118 AC XY: 64501 AN XY: 544346

Gnomad4 AFR exome AF: 0.0865

Gnomad4 AMR exome AF: 0.163

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.533

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.481

Gnomad4 NFE exome AF: 0.0802

Gnomad4 OTH exome AF: 0.166

GnomAD4 genome AF: 0.485 AC: 54727 AN: 112786 Hom.: 12582 Cov.: 0 AF XY: 0.489 AC XY: 26463 AN XY: 54152

Gnomad4 AFR AF: 0.407

Gnomad4 AMR AF: 0.477

Gnomad4 ASJ AF: 0.502

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.479

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jan 23, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71170559; hg19: chr19-13875539;