rs11638130

Variant names:

• chr15-74891594-G-A
• rs11638130
• NM_002435.3:c.345+15G>A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002435.3(MPI):​c.345+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,612,402 control chromosomes in the GnomAD database, including 195,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.35 (12205 hom., cov: 32)
  • Exomes 𝑓: 0.48 (183379 hom.)
• Consequence: MPI NM_002435.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.570

Genes affected

MPI (HGNC:7216): (mannose phosphate isomerase) Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 15-74891594-G-A is Benign according to our data. Variant chr15-74891594-G-A is described in ClinVar as [Benign]. Clinvar id is 94067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-74891594-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPI	NM_002435.3	c.345+15G>A		intron_variant	Intron 3 of 7	ENST00000352410.9	NP_002426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPI	ENST00000352410.9	c.345+15G>A		intron_variant	Intron 3 of 7	1	NM_002435.3	ENSP00000318318.6

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53529 AN: 151998 Hom.: 12206 Cov.: 32

Gnomad AFR AF: 0.0970

Gnomad AMI AF: 0.385

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.519

Gnomad OTH AF: 0.359

GnomAD3 exomes AF: 0.374 AC: 93905 AN: 251194 Hom.: 21210 AF XY: 0.370 AC XY: 50312 AN XY: 135802

Gnomad AFR exome AF: 0.0859

Gnomad AMR exome AF: 0.349

Gnomad ASJ exome AF: 0.395

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.131

Gnomad FIN exome AF: 0.402

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.423

GnomAD4 exome AF: 0.480 AC: 701545 AN: 1460286 Hom.: 183379 Cov.: 34 AF XY: 0.470 AC XY: 341447 AN XY: 726522

Gnomad4 AFR exome AF: 0.0823

Gnomad4 AMR exome AF: 0.361

Gnomad4 ASJ exome AF: 0.396

Gnomad4 EAS exome AF: 0.131

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.410

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.435

GnomAD4 genome AF: 0.352 AC: 53535 AN: 152116 Hom.: 12205 Cov.: 32 AF XY: 0.341 AC XY: 25330 AN XY: 74344

Gnomad4 AFR AF: 0.0967

Gnomad4 AMR AF: 0.409

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.519

Gnomad4 OTH AF: 0.359

Alfa AF: 0.470 Hom.: 18145

Bravo AF: 0.349

Asia WGS AF: 0.121 AC: 424 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

Jul 10, 2012

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Dec 02, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 37% of total chromosomes in ExAC -

MPI-congenital disorder of glycosylation Benign:4

Jul 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.70
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11638130; hg19: chr15-75183935; COSMIC: COSV60396824; COSMIC: COSV60396824;