19-13764725-AGCGGGGCG-A

Variant summary

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

The NM_001031727.4(MRI1):c.133-71_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 0.00545 in 1,236,474 control chromosomes in the GnomAD database, including 205 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.061 (204 hom., cov: 0)
  • Exomes 𝑓: 0.000012 (1 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-AGCGGGGCG-A is Benign according to our data. Variant chr19-13764725-AGCGGGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2014921.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRI1	NM_001031727.4	c.133-71_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.133-71_133-64del		splice_donor_region_variant, intron_variant		1	NM_001031727.4	P1

Frequencies

GnomAD3 genomes AF: 0.0606 AC: 6729 AN: 111014 Hom.: 203 Cov.: 0

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.0266

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.0664

Gnomad EAS AF: 0.0319

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0392

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0704

GnomAD4 exome AF: 0.0000124 AC: 14 AN: 1125386 Hom.: 1 AF XY: 0.0000129 AC XY: 7 AN XY: 544378

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000286

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000108

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0606 AC: 6727 AN: 111088 Hom.: 204 Cov.: 0 AF XY: 0.0597 AC XY: 3186 AN XY: 53354

Gnomad4 AFR AF: 0.0297

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.0664

Gnomad4 EAS AF: 0.0320

Gnomad4 SAS AF: 0.0701

Gnomad4 FIN AF: 0.0392

Gnomad4 NFE AF: 0.0738

Gnomad4 OTH AF: 0.0696

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

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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;