Variant rs12593975 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002435.3(MPI):c.1053+31G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0846 in 1,606,660 control chromosomes in the GnomAD database, including 11,890 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.087 ( 1053 hom., cov: 32)

Exomes 𝑓: 0.084 ( 10837 hom. )

Consequence

MPI
NM_002435.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.893

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BP6

Variant 15-74897250-G-A is Benign according to our data. Variant chr15-74897250-G-A is described in ClinVar as [Benign]. Clinvar id is 258656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.346 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.1053+31G>A		intron_variant		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.1053+31G>A		intron_variant		1	NM_002435.3	ENSP00000318318.6		P34949-1

Frequencies

GnomAD3 genomes

AF:

0.0865

AC:

13160

AN:

152086

Hom.:

1054

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.127

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.0657

Gnomad EAS

AF:

0.352

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0514

Gnomad OTH

AF:

0.0952

GnomAD3 exomes

AF:

0.137

AC:

34169

AN:

250300

Hom.:

4194

AF XY:

0.142

AC XY:

19204

AN XY:

135408

show subpopulations

Gnomad AFR exome

AF:

0.0642

Gnomad AMR exome

AF:

0.192

Gnomad ASJ exome

AF:

0.0661

Gnomad EAS exome

AF:

0.360

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.103

Gnomad NFE exome

AF:

0.0529

Gnomad OTH exome

AF:

0.117

GnomAD4 exome

AF:

0.0844

AC:

122786

AN:

1454456

Hom.:

10837

Cov.:

AF XY:

0.0913

AC XY:

66108

AN XY:

724056

show subpopulations

Gnomad4 AFR exome

AF:

0.0591

Gnomad4 AMR exome

AF:

0.180

Gnomad4 ASJ exome

AF:

0.0661

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.336

Gnomad4 FIN exome

AF:

0.101

Gnomad4 NFE exome

AF:

0.0511

Gnomad4 OTH exome

AF:

0.103

GnomAD4 genome

AF:

0.0865

AC:

13171

AN:

152204

Hom.:

1053

Cov.:

AF XY:

0.0952

AC XY:

7087

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.0657

Gnomad4 EAS

AF:

0.353

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.109

Gnomad4 NFE

AF:

0.0514

Gnomad4 OTH

AF:

0.0956

Alfa

AF:

0.0747

Hom.:

220

Bravo

AF:

0.0824

Asia WGS

AF:

0.371

AC:

1287

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

MPI-congenital disorder of glycosylation

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.48

DANN

Benign

0.83

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