19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-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+56_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 0.0111 in 1,237,512 control chromosomes in the GnomAD database, including 1,318 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.065 (389 hom., cov: 0)
  • Exomes 𝑓: 0.0058 (929 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-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A is Benign according to our data. Variant chr19-13764725-AGCGGGGCGGCGGGGCGGCGGGGCGGCGGGGCG-A is described in ClinVar as [Likely_benign]. Clinvar id is 2126057.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MRI1	NM_001031727.4	c.132+56_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+56_133-64del		splice_donor_region_variant, intron_variant		1	NM_001031727.4	P1

Frequencies

GnomAD3 genomes AF: 0.0649 AC: 7311 AN: 112594 Hom.: 390 Cov.: 0

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.0405

Gnomad ASJ AF: 0.0354

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.0461

Gnomad MID AF: 0.0402

Gnomad NFE AF: 0.0402

Gnomad OTH AF: 0.0585

GnomAD4 exome AF: 0.00576 AC: 6479 AN: 1124838 Hom.: 929 AF XY: 0.00615 AC XY: 3344 AN XY: 544116

Gnomad4 AFR exome AF: 0.0203

Gnomad4 AMR exome AF: 0.00813

Gnomad4 ASJ exome AF: 0.0114

Gnomad4 EAS exome AF: 0.0132

Gnomad4 SAS exome AF: 0.000814

Gnomad4 FIN exome AF: 0.0276

Gnomad4 NFE exome AF: 0.00450

Gnomad4 OTH exome AF: 0.0106

GnomAD4 genome AF: 0.0649 AC: 7313 AN: 112674 Hom.: 389 Cov.: 0 AF XY: 0.0640 AC XY: 3462 AN XY: 54110

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.0405

Gnomad4 ASJ AF: 0.0354

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.0134

Gnomad4 FIN AF: 0.0461

Gnomad4 NFE AF: 0.0402

Gnomad4 OTH AF: 0.0578

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

Oct 11, 2023

- -

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;