rs10852891

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.685G>A(p.Ala229Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 1,613,126 control chromosomes in the GnomAD database, including 22,184 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 1918 hom., cov: 29)

Exomes 𝑓: 0.16 ( 20266 hom. )

Consequence

MPDU1
NM_004870.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.903

Publications

38 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=0.0021248758).

BP6

Variant 17-7587492-G-A is Benign according to our data. Variant chr17-7587492-G-A is described in ClinVar as Benign. ClinVar VariationId is 95181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.173 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004870.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDU1	NM_004870.4	MANE Select	c.685G>A	p.Ala229Thr	missense	Exon 7 of 7	NP_004861.2
MPDU1	NR_024603.1		n.896G>A		non_coding_transcript_exon	Exon 7 of 7
MPDU1	NM_001330073.1		c.*48G>A		3_prime_UTR	Exon 6 of 6	NP_001317002.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MPDU1	ENST00000250124.11	TSL:1 MANE Select	c.685G>A	p.Ala229Thr	missense	Exon 7 of 7	ENSP00000250124.6
MPDU1	ENST00000571877.1	TSL:1	n.870G>A		non_coding_transcript_exon	Exon 2 of 2
MPDU1	ENST00000359822.10	TSL:3	n.*436G>A		non_coding_transcript_exon	Exon 6 of 6	ENSP00000352876.6

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23696

AN:

151208

Hom.:

1911

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.165

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.180

Gnomad EAS

AF:

0.157

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.147

GnomAD2 exomes

AF:

0.148

AC:

37145

AN:

251360

AF XY:

0.149

show subpopulations

Gnomad AFR exome

AF:

0.176

Gnomad AMR exome

AF:

0.0951

Gnomad ASJ exome

AF:

0.180

Gnomad EAS exome

AF:

0.160

Gnomad FIN exome

AF:

0.0909

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.164

AC:

240080

AN:

1461800

Hom.:

20266

Cov.:

AF XY:

0.163

AC XY:

118352

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.180

AC:

6021

AN:

33480

American (AMR)

AF:

0.0975

AC:

4359

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

4715

AN:

26136

East Asian (EAS)

AF:

0.169

AC:

6706

AN:

39696

South Asian (SAS)

AF:

0.148

AC:

12725

AN:

86258

European-Finnish (FIN)

AF:

0.0956

AC:

5102

AN:

53386

Middle Eastern (MID)

AF:

0.118

AC:

680

AN:

5768

European-Non Finnish (NFE)

AF:

0.171

AC:

189755

AN:

1111968

Other (OTH)

AF:

0.166

AC:

10017

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

12039

24079

36118

48158

60197

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6864

13728

20592

27456

34320

<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:

0.157

AC:

23715

AN:

151326

Hom.:

1918

Cov.:

AF XY:

0.152

AC XY:

11267

AN XY:

73922

show subpopulations

African (AFR)

AF:

0.176

AC:

7268

AN:

41184

American (AMR)

AF:

0.124

AC:

1887

AN:

15162

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

625

AN:

3464

East Asian (EAS)

AF:

0.157

AC:

795

AN:

5078

South Asian (SAS)

AF:

0.159

AC:

762

AN:

4790

European-Finnish (FIN)

AF:

0.0816

AC:

856

AN:

10490

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11041

AN:

67860

Other (OTH)

AF:

0.149

AC:

312

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

982

1963

2945

3926

4908

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<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:

0.157

Hom.:

4706

Bravo

AF:

0.164

TwinsUK

AF:

0.172

AC:

637

ALSPAC

AF:

0.171

AC:

658

ESP6500AA

AF:

0.177

AC:

778

ESP6500EA

AF:

0.167

AC:

1439

ExAC

AF:

0.154

AC:

18675

Asia WGS

AF:

0.176

AC:

612

AN:

3478

EpiCase

AF:

0.158

EpiControl

AF:

0.160

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

MPDU1-congenital disorder of glycosylation (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0043

Eigen

Benign

-0.053

Eigen_PC

Benign

-0.090

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.59

MetaRNN

Benign

0.0021

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PhyloP100

0.90

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.13

Sift

Benign

0.21

Sift4G

Benign

0.38

Polyphen

0.60

Vest4

0.082

MPC

0.35

ClinPred

0.0043

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.025

gMVP

0.31

Mutation Taster

=88/12

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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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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over