19-13764725-A-AGCGGGGCG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001031727.4(MRI1):c.133-71_133-64dup variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.0021 (1 hom., cov: 0)
• Consequence: MRI1 NM_001031727.4 splice_donor_region, intron
• Clinical Significance: 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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 19-13764725-A-AGCGGGGCG is Benign according to our data. Variant chr19-13764725-A-AGCGGGGCG is described in ClinVar as [Benign]. Clinvar id is 2007650.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00214 AC: 241 AN: 112650 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00142

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00272

Gnomad ASJ AF: 0.00451

Gnomad EAS AF: 0.000485

Gnomad SAS AF: 0.000298

Gnomad FIN AF: 0.000162

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00280

Gnomad OTH AF: 0.00272

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00214 AC: 241 AN: 112728 Hom.: 1 Cov.: 0 AF XY: 0.00174 AC XY: 94 AN XY: 54126

Gnomad4 AFR AF: 0.00142

Gnomad4 AMR AF: 0.00271

Gnomad4 ASJ AF: 0.00451

Gnomad4 EAS AF: 0.000488

Gnomad4 SAS AF: 0.000298

Gnomad4 FIN AF: 0.000162

Gnomad4 NFE AF: 0.00280

Gnomad4 OTH AF: 0.00269

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

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;