rs16956808
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1
The NM_004870.4(MPDU1):c.673G>A(p.Gly225Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,613,490 control chromosomes in the GnomAD database, including 431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.030 ( 218 hom., cov: 30)
Exomes 𝑓: 0.0032 ( 213 hom. )
Consequence
MPDU1
NM_004870.4 missense
NM_004870.4 missense
Scores
7
11
Clinical Significance
Conservation
PhyloP100: 7.76
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
?
Variant 17-7587480-G-A is Benign according to our data. Variant chr17-7587480-G-A is described in ClinVar as [Benign]. Clinvar id is 325520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPDU1 | NM_004870.4 | c.673G>A | p.Gly225Ser | missense_variant | 7/7 | ENST00000250124.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPDU1 | ENST00000250124.11 | c.673G>A | p.Gly225Ser | missense_variant | 7/7 | 1 | NM_004870.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0304 AC: 4603AN: 151504Hom.: 218 Cov.: 30
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GnomAD3 exomes AF: 0.00791 AC: 1989AN: 251388Hom.: 98 AF XY: 0.00573 AC XY: 779AN XY: 135884
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GnomAD4 exome AF: 0.00316 AC: 4615AN: 1461866Hom.: 213 Cov.: 33 AF XY: 0.00272 AC XY: 1980AN XY: 727232
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GnomAD4 genome ? AF: 0.0304 AC: 4604AN: 151624Hom.: 218 Cov.: 30 AF XY: 0.0295 AC XY: 2186AN XY: 74064
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
MPDU1-congenital disorder of glycosylation Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 10, 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. - |
MPDU1-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 24, 2020 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: 2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at