9-13107066-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001378778.1(MPDZ):āc.6112A>Gā(p.Ile2038Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000374 in 1,602,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001378778.1 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 rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPDZ | NM_001378778.1 | c.6112A>G | p.Ile2038Val | missense_variant | Exon 47 of 47 | ENST00000319217.12 | NP_001365707.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248912Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134998
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1450002Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 720220
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74384
ClinVar
Submissions by phenotype
MPDZ-related disorder Uncertain:1
The MPDZ c.6025A>G variant is predicted to result in the amino acid substitution p.Ile2009Val. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.019% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-13107065-T-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
not provided Uncertain:1
This variant is present in population databases (rs369284040, gnomAD 0.02%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 2009 of the MPDZ protein (p.Ile2009Val). 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with MPDZ-related conditions. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at