chr17-7586913-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004870.4(MPDU1):c.403G>C(p.Ala135Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00164 in 1,613,988 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A135T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 14 hom., cov: 31)

Exomes 𝑓: 0.0015 ( 56 hom. )

Consequence

MPDU1
NM_004870.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 3.08

Publications

6 publications found

Variant links:

Genes affected

MPDU1 (HGNC:7207): (mannose-P-dolichol utilization defect 1) This gene encodes an endoplasmic reticulum membrane protein that is required for utilization of the mannose donor mannose-P-dolichol in the synthesis of lipid-linked oligosaccharides and glycosylphosphatidylinositols. Mutations in this gene result in congenital disorder of glycosylation type If. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

MPDU1 Gene-Disease associations (from GenCC):

MPDU1-congenital disorder of glycosylation
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Orphanet, G2P

MPDU1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003244996).

BP6

Variant 17-7586913-G-C is Benign according to our data. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7586913-G-C is described in CliVar as Benign. Clinvar id is 95180.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0525 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPDU1	NM_004870.4 link	c.403G>C	p.Ala135Pro	missense_variant	Exon 5 of 7	ENST00000250124.11	NP_004861.2	O75352-1A0A0S2Z4W8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000250124.11 link	c.403G>C	p.Ala135Pro	missense_variant	Exon 5 of 7	1	NM_004870.4	ENSP00000250124.6		O75352-1

Frequencies

GnomAD3 genomes

AF:

0.00260

AC:

396

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0577

Gnomad SAS

AF:

0.00436

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00478

GnomAD2 exomes

AF:

0.00445

AC:

1118

AN:

251256

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0551

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00154

AC:

2253

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1107

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.000747

AC:

AN:

33480

American (AMR)

AF:

0.000112

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0401

AC:

1593

AN:

39700

South Asian (SAS)

AF:

0.00262

AC:

226

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000216

AC:

AN:

1112008

Other (OTH)

AF:

0.00628

AC:

379

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

160

200

<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:

0.00260

AC:

395

AN:

152158

Hom.:

Cov.:

AF XY:

0.00294

AC XY:

219

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00135

AC:

AN:

41480

American (AMR)

AF:

0.000589

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.0579

AC:

299

AN:

5166

South Asian (SAS)

AF:

0.00436

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68004

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.00179

Hom.:

Bravo

AF:

0.00247

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00419

AC:

509

Asia WGS

AF:

0.0310

AC:

109

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 06, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 17, 2017

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. -

MPDU1-congenital disorder of glycosylation

Benign:2

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 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. -

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

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.060

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.1

M;.

PhyloP100

3.1

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.5

N;.

REVEL

Uncertain

0.50

Sift

Benign

0.082

T;.

Sift4G

Benign

0.19

T;T

Polyphen

0.0080

B;.

Vest4

0.74

MVP

0.77

MPC

0.47

ClinPred

0.033

GERP RS

4.5

Varity_R

0.24

gMVP

0.84

Mutation Taster

=92/8

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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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