rs148935720
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_004870.4(MPDU1):c.43C>T(p.Pro15Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,614,196 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004870.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPDU1 | NM_004870.4 | c.43C>T | p.Pro15Ser | missense_variant | Exon 1 of 7 | ENST00000250124.11 | NP_004861.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00107 AC: 163AN: 152248Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000314 AC: 79AN: 251320Hom.: 0 AF XY: 0.000184 AC XY: 25AN XY: 135856
GnomAD4 exome AF: 0.000119 AC: 174AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.000100 AC XY: 73AN XY: 727214
GnomAD4 genome AF: 0.00106 AC: 162AN: 152366Hom.: 0 Cov.: 33 AF XY: 0.000966 AC XY: 72AN XY: 74516
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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MPDU1-congenital disorder of glycosylation Uncertain:1Benign:1
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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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -
not specified Uncertain:1
Variant summary: MPDU1 c.43C>T (p.Pro15Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 251320 control chromosomes (gnomAD). To our knowledge, no occurrence of c.43C>T in individuals affected with Congenital Disorder Of Glycosylation, Type I and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=2) or likely benign (n=2). Based on the evidence outlined above, the variant was classified as uncertain significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at