17-7583881-G-T
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_StrongPM2PP5
The NM_004870.4(MPDU1):c.19G>T(p.Gly7*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,994 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004870.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPDU1 | NM_004870.4 | c.19G>T | p.Gly7* | stop_gained | Exon 1 of 7 | ENST00000250124.11 | NP_004861.2 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251212Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135822
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461744Hom.: 0 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727188
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152250Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74382
ClinVar
Submissions by phenotype
MPDU1-congenital disorder of glycosylation Uncertain:1Other:1
Variant interpretted as Likely pathogenic and reported on 07/25/2018 by GTR ID PerkinElmer Genetics, Inc.. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
This sequence change creates a premature translational stop signal (p.Gly7*) in the MPDU1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in MPDU1 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MPDU1-related conditions. ClinVar contains an entry for this variant (Variation ID: 684508). 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. -
Inborn genetic diseases Pathogenic:1
The c.19G>T (p.G7*) alteration, located in exon 1 (coding exon 1) of the MPDU1 gene, consists of a G to T substitution at nucleotide position 19. This changes the amino acid from a glycine (G) to a stop codon at amino acid position 7. The predicted stop codon occurs within the first 150 nucleotides of the MPDU1 gene. This alteration may escape nonsense-mediated mRNA decay and/or be rescued by re-initiation (Rivas, 2015; Lindeboom, 2016; Rhee, 2017). However, a significant portion of the protein is affected (Ambry internal data). Based on the available evidence, this alteration is classified as likely pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at