rs10852891

Positions:

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 95181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-7587492-G-A is described in Lovd as [Benign].

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPDU1	NM_004870.4 linkuse as main transcript	c.685G>A	p.Ala229Thr	missense_variant	7/7	ENST00000250124.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPDU1	ENST00000250124.11 linkuse as main transcript	c.685G>A	p.Ala229Thr	missense_variant	7/7	1	NM_004870.4	P1	O75352-1

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

GnomAD3 exomes

AF:

0.148

AC:

37145

AN:

251360

Hom.:

2932

AF XY:

0.149

AC XY:

20182

AN XY:

135872

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 SAS exome

AF:

0.148

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

Gnomad4 AFR exome

AF:

0.180

Gnomad4 AMR exome

AF:

0.0975

Gnomad4 ASJ exome

AF:

0.180

Gnomad4 EAS exome

AF:

0.169

Gnomad4 SAS exome

AF:

0.148

Gnomad4 FIN exome

AF:

0.0956

Gnomad4 NFE exome

AF:

0.171

Gnomad4 OTH exome

AF:

0.166

GnomAD4 genome

AF:

0.157

AC:

23715

AN:

151326

Hom.:

1918

Cov.:

AF XY:

0.152

AC XY:

11267

AN XY:

73922

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.124

Gnomad4 ASJ

AF:

0.180

Gnomad4 EAS

AF:

0.157

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.0816

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.149

Alfa

AF:

0.155

Hom.:

3039

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

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 02, 2015	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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jul 26, 2012	- -

MPDU1-congenital disorder of glycosylation

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.48

CADD

Benign

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

MutationTaster

Benign

0.33

P;P;P

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

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