dbSNP rs12593975: MPI:c.1053+31G>A (chr15-74897250-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

4 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), Myriad Women's Health, G2P, Orphanet, ClinGen

MPI links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002435.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002435.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPI	NM_002435.3	MANE Select	c.1053+31G>A	intron	N/A	NP_002426.1	P34949-1
MPI	NM_001330372.2		c.993+31G>A	intron	N/A	NP_001317301.1	H3BPB8
MPI	NM_001289156.2		c.903+31G>A	intron	N/A	NP_001276085.1	F5GX71

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MPI	ENST00000352410.9	TSL:1 MANE Select	c.1053+31G>A	intron	N/A	ENSP00000318318.6	P34949-1
MPI	ENST00000323744.10	TSL:1	c.870+31G>A	intron	N/A	ENSP00000318192.6	P34949-2
MPI	ENST00000566377.5	TSL:1	c.845-262G>A	intron	N/A	ENSP00000455405.1	H3BPP3

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

GnomAD2 exomes

AF:

0.137

AC:

34169

AN:

250300

AF XY:

0.142

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 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

African (AFR)

AF:

0.0591

AC:

1972

AN:

33350

American (AMR)

AF:

0.180

AC:

8053

AN:

44688

Ashkenazi Jewish (ASJ)

AF:

0.0661

AC:

1727

AN:

26110

East Asian (EAS)

AF:

0.342

AC:

13561

AN:

39662

South Asian (SAS)

AF:

0.336

AC:

28878

AN:

86068

European-Finnish (FIN)

AF:

0.101

AC:

5348

AN:

53034

Middle Eastern (MID)

AF:

0.0957

AC:

551

AN:

5758

European-Non Finnish (NFE)

AF:

0.0511

AC:

56518

AN:

1105636

Other (OTH)

AF:

0.103

AC:

6178

AN:

60150

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

5765

11530

17296

23061

28826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2576

5152

7728

10304

12880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0865

AC:

13171

AN:

152204

Hom.:

1053

Cov.:

AF XY:

0.0952

AC XY:

7087

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.0624

AC:

2591

AN:

41528

American (AMR)

AF:

0.118

AC:

1801

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0657

AC:

228

AN:

3470

East Asian (EAS)

AF:

0.353

AC:

1825

AN:

5174

South Asian (SAS)

AF:

0.360

AC:

1735

AN:

4818

European-Finnish (FIN)

AF:

0.109

AC:

1155

AN:

10600

Middle Eastern (MID)

AF:

0.0816

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0514

AC:

3494

AN:

68004

Other (OTH)

AF:

0.0956

AC:

202

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

558

1116

1673

2231

2789

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

170

340

510

680

850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0715

Hom.:

239

Bravo

AF:

0.0824

Asia WGS

AF:

0.371

AC:

1287

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

MPI-congenital disorder of glycosylation (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.48

(source)

DANN

Benign

0.83

PhyloP100

-0.89

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over