rs137983973
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004870.4(MPDU1):c.403G>A(p.Ala135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,613,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004870.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPDU1 | NM_004870.4 | c.403G>A | p.Ala135Thr | missense_variant | 5/7 | ENST00000250124.11 | NP_004861.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPDU1 | ENST00000250124.11 | c.403G>A | p.Ala135Thr | missense_variant | 5/7 | 1 | NM_004870.4 | ENSP00000250124.6 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152040Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251256Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135836
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461830Hom.: 0 Cov.: 33 AF XY: 0.00000550 AC XY: 4AN XY: 727230
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152040Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74258
ClinVar
Submissions by phenotype
MPDU1-congenital disorder of glycosylation Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 18, 2019 | This variant is present in population databases (rs137983973, ExAC 0.003%). This sequence change replaces alanine with threonine at codon 135 of the MPDU1 protein (p.Ala135Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant has not been reported in the literature in individuals with MPDU1-related conditions. 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at