rs139190144
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Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1
The NM_002435.3(MPI):c.684C>T(p.Asn228=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,614,080 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.021 ( 60 hom., cov: 32)
Exomes 𝑓: 0.029 ( 826 hom. )
Consequence
MPI
NM_002435.3 synonymous
NM_002435.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.96
Genes affected
MPI (HGNC:7216): (mannose phosphate isomerase) Phosphomannose isomerase catalyzes the interconversion of fructose-6-phosphate and mannose-6-phosphate and plays a critical role in maintaining the supply of D-mannose derivatives, which are required for most glycosylation reactions. Mutations in the MPI gene were found in patients with carbohydrate-deficient glycoprotein syndrome, type Ib. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.45).
BP6
?
Variant 15-74896165-C-T is Benign according to our data. Variant chr15-74896165-C-T is described in ClinVar as [Benign]. Clinvar id is 167305.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-74896165-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.96 with no splicing effect.
BA1
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GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPI | NM_002435.3 | c.684C>T | p.Asn228= | synonymous_variant | 6/8 | ENST00000352410.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPI | ENST00000352410.9 | c.684C>T | p.Asn228= | synonymous_variant | 6/8 | 1 | NM_002435.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0213 AC: 3240AN: 152140Hom.: 60 Cov.: 32
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GnomAD3 exomes AF: 0.0254 AC: 6388AN: 251398Hom.: 155 AF XY: 0.0287 AC XY: 3899AN XY: 135872
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GnomAD4 exome AF: 0.0288 AC: 42143AN: 1461822Hom.: 826 Cov.: 31 AF XY: 0.0301 AC XY: 21902AN XY: 727204
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GnomAD4 genome ? AF: 0.0213 AC: 3242AN: 152258Hom.: 60 Cov.: 32 AF XY: 0.0225 AC XY: 1677AN XY: 74438
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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 | Eurofins Ntd Llc (ga) | Jan 14, 2014 | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 27, 2016 | 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. - |
MPI-congenital disorder of glycosylation Benign:3
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. - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
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RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at