Variant rs1130741 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002435.3(MPI):c.1131A>G(p.Val377Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 1,613,846 control chromosomes in the GnomAD database, including 219,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16292 hom., cov: 32)

Exomes 𝑓: 0.52 ( 202972 hom. )

Consequence

MPI
NM_002435.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.478

Variant links:

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]

MPI links:

MPI (HGNC:):

MPI links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant 15-74897589-A-G is Benign according to our data. Variant chr15-74897589-A-G is described in ClinVar as [Benign]. Clinvar id is 94066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-74897589-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.478 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPI	NM_002435.3 linkuse as main transcript	c.1131A>G	p.Val377Val	synonymous_variant	8/8	ENST00000352410.9	NP_002426.1	P34949-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPI	ENST00000352410.9 linkuse as main transcript	c.1131A>G	p.Val377Val	synonymous_variant	8/8	1	NM_002435.3	ENSP00000318318.6		P34949-1

Frequencies

GnomAD3 genomes

AF:

0.449

AC:

68180

AN:

151932

Hom.:

16271

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.433

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.469

Gnomad EAS

AF:

0.230

Gnomad SAS

AF:

0.192

Gnomad FIN

AF:

0.430

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.538

Gnomad OTH

AF:

0.442

GnomAD3 exomes

AF:

0.445

AC:

111822

AN:

251392

Hom.:

27095

AF XY:

0.435

AC XY:

59083

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.332

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.462

Gnomad EAS exome

AF:

0.220

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.432

Gnomad NFE exome

AF:

0.539

Gnomad OTH exome

AF:

0.473

GnomAD4 exome

AF:

0.515

AC:

753438

AN:

1461796

Hom.:

202972

Cov.:

AF XY:

0.505

AC XY:

367431

AN XY:

727218

show subpopulations

Gnomad4 AFR exome

AF:

0.331

Gnomad4 AMR exome

AF:

0.523

Gnomad4 ASJ exome

AF:

0.468

Gnomad4 EAS exome

AF:

0.245

Gnomad4 SAS exome

AF:

0.208

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.561

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.449

AC:

68256

AN:

152050

Hom.:

16292

Cov.:

AF XY:

0.439

AC XY:

32586

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.469

Gnomad4 EAS

AF:

0.230

Gnomad4 SAS

AF:

0.192

Gnomad4 FIN

AF:

0.430

Gnomad4 NFE

AF:

0.538

Gnomad4 OTH

AF:

0.443

Alfa

AF:

0.512

Hom.:

42943

Bravo

AF:

0.458

Asia WGS

AF:

0.229

AC:

800

AN:

3478

EpiCase

AF:

0.524

EpiControl

AF:

0.524

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	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: 44% of total chromosomes in ExAC -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 10, 2012	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -

MPI-congenital disorder of glycosylation

Benign:5

Benign, no assertion criteria provided	clinical testing	Natera, Inc.	Sep 16, 2020	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

7.4

DANN

Benign

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over