Variant chr17-7583872-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004870.4(MPDU1):c.10G>A(p.Glu4Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000479 in 1,461,704 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MPDU1
NM_004870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.63

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:

MPDU1-AS1 (HGNC:40379): (MPDU1 antisense RNA 1)

MPDU1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41885367).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MPDU1	NM_004870.4 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant	1/7	ENST00000250124.11	NP_004861.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MPDU1	ENST00000250124.11 linkuse as main transcript	c.10G>A	p.Glu4Lys	missense_variant	1/7	1	NM_004870.4	ENSP00000250124	P1	O75352-1
MPDU1-AS1	ENST00000655859.2 linkuse as main transcript	n.181+46C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250768

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135662

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461704

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MPDU1-congenital disorder of glycosylation

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

May 23, 2018

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with MPDU1-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glutamic acid with lysine at codon 4 of the MPDU1 protein (p.Glu4Lys). The glutamic acid residue is moderately conserved and there is a small physicochemical difference between glutamic acid and lysine. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Pathogenic

0.25

BayesDel_noAF

Pathogenic

0.29

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0027

.;T;.;.;.;T

Eigen

Benign

0.13

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.92

D;D;D;D;D;D

M_CAP

Benign

0.077

MetaRNN

Benign

0.42

T;T;T;T;T;T

MetaSVM

Uncertain

0.57

MutationAssessor

Benign

1.9

.;L;.;.;L;.

MutationTaster

Benign

0.88

D;D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-1.2

.;N;N;.;N;.

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

.;D;D;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

0.96

.;D;.;.;.;.

Vest4

0.34

MutPred

0.17

Gain of ubiquitination at E4 (P = 0.0325);Gain of ubiquitination at E4 (P = 0.0325);Gain of ubiquitination at E4 (P = 0.0325);Gain of ubiquitination at E4 (P = 0.0325);Gain of ubiquitination at E4 (P = 0.0325);Gain of ubiquitination at E4 (P = 0.0325);

MVP

0.86

MPC

0.40

ClinPred

0.96

GERP RS

5.3

Varity_R

0.46

gMVP

0.79

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