rs755060398
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_001378778.1(MPDZ):c.1894C>T(p.Arg632Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000596 in 1,610,562 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R632G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001378778.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPDZ | NM_001378778.1 | c.1894C>T | p.Arg632Cys | missense_variant | 15/47 | ENST00000319217.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPDZ | ENST00000319217.12 | c.1894C>T | p.Arg632Cys | missense_variant | 15/47 | 5 | NM_001378778.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152042Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000902 AC: 22AN: 243798Hom.: 1 AF XY: 0.0000984 AC XY: 13AN XY: 132066
GnomAD4 exome AF: 0.0000624 AC: 91AN: 1458520Hom.: 1 Cov.: 31 AF XY: 0.0000676 AC XY: 49AN XY: 725162
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152042Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 2022 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 632 of the MPDZ protein (p.Arg632Cys). This variant is present in population databases (rs755060398, gnomAD 0.03%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with MPDZ-related conditions. ClinVar contains an entry for this variant (Variation ID: 377077). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Nov 03, 2016 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Apr 27, 2019 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 17, 2023 | The c.1894C>T (p.R632C) alteration is located in exon 14 (coding exon 14) of the MPDZ gene. This alteration results from a C to T substitution at nucleotide position 1894, causing the arginine (R) at amino acid position 632 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at