19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCG-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+64_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 0.00963 in 1,233,066 control chromosomes in the GnomAD database, including 816 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.085 (554 hom., cov: 0)
  • Exomes 𝑓: 0.0021 (262 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-AGCGGGGCGGCGGGGCGGCGGGGCG-A is Benign according to our data. Variant chr19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 1995433.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0864 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 9499 AN: 112124 Hom.: 554 Cov.: 0

Gnomad AFR AF: 0.0842

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0942

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0633

Gnomad MID AF: 0.0991

Gnomad NFE AF: 0.0872

Gnomad OTH AF: 0.0978

GnomAD4 exome AF: 0.00211 AC: 2366 AN: 1120864 Hom.: 262 AF XY: 0.00239 AC XY: 1296 AN XY: 542060

Gnomad4 AFR exome AF: 0.00278

Gnomad4 AMR exome AF: 0.00444

Gnomad4 ASJ exome AF: 0.00343

Gnomad4 EAS exome AF: 0.00457

Gnomad4 SAS exome AF: 0.00101

Gnomad4 FIN exome AF: 0.0120

Gnomad4 NFE exome AF: 0.00171

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.0847 AC: 9506 AN: 112202 Hom.: 554 Cov.: 0 AF XY: 0.0843 AC XY: 4541 AN XY: 53842

Gnomad4 AFR AF: 0.0843

Gnomad4 AMR AF: 0.0854

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0942

Gnomad4 SAS AF: 0.0467

Gnomad4 FIN AF: 0.0633

Gnomad4 NFE AF: 0.0871

Gnomad4 OTH AF: 0.0959

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 18, 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;