chr15-74897589-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

39 publications found

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 Gene-Disease associations (from GenCC):

MPI-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, PanelApp Australia, Myriad Women’s Health, G2P, ClinGen

MPI links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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 rank	MANE	Protein	UniProt
MPI	NM_002435.3 link	c.1131A>G	p.Val377Val	synonymous_variant	Exon 8 of 8	ENST00000352410.9	NP_002426.1	P34949-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPI	ENST00000352410.9 link	c.1131A>G	p.Val377Val	synonymous_variant	Exon 8 of 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

GnomAD2 exomes

AF:

0.445

AC:

111822

AN:

251392

AF XY:

0.435

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 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

African (AFR)

AF:

0.331

AC:

11067

AN:

33480

American (AMR)

AF:

0.523

AC:

23365

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.468

AC:

12220

AN:

26136

East Asian (EAS)

AF:

0.245

AC:

9730

AN:

39698

South Asian (SAS)

AF:

0.208

AC:

17946

AN:

86258

European-Finnish (FIN)

AF:

0.438

AC:

23399

AN:

53418

Middle Eastern (MID)

AF:

0.407

AC:

2348

AN:

5768

European-Non Finnish (NFE)

AF:

0.561

AC:

624200

AN:

1111926

Other (OTH)

AF:

0.483

AC:

29163

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

21941

43882

65822

87763

109704

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.449

AC:

68256

AN:

152050

Hom.:

16292

Cov.:

AF XY:

0.439

AC XY:

32586

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.339

AC:

14081

AN:

41486

American (AMR)

AF:

0.515

AC:

7869

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.469

AC:

1627

AN:

3470

East Asian (EAS)

AF:

0.230

AC:

1189

AN:

5172

South Asian (SAS)

AF:

0.192

AC:

925

AN:

4816

European-Finnish (FIN)

AF:

0.430

AC:

4538

AN:

10546

Middle Eastern (MID)

AF:

0.415

AC:

122

AN:

294

European-Non Finnish (NFE)

AF:

0.538

AC:

36573

AN:

67962

Other (OTH)

AF:

0.443

AC:

937

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1896

3793

5689

7586

9482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.502

Hom.:

59839

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

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 10, 2012

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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: 44% of total chromosomes in ExAC -

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. -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

MPI-congenital disorder of glycosylation

Benign:5

Sep 16, 2020

Natera, Inc.

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Jul 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

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

-0.61

CADD

Benign

7.4

(source)

DANN

Benign

0.68

PhyloP100

0.48

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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chr15-74897589-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over