rs758473798
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001378778.1(MPDZ):c.2401G>T(p.Asp801Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.0000818 in 1,588,910 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000084 ( 1 hom. )
Consequence
MPDZ
NM_001378778.1 missense
NM_001378778.1 missense
Scores
10
9
Clinical Significance
Conservation
PhyloP100: 3.90
Genes affected
MPDZ (HGNC:7208): (multiple PDZ domain crumbs cell polarity complex component) The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MPDZ | NM_001378778.1 | c.2401G>T | p.Asp801Tyr | missense_variant | 18/47 | ENST00000319217.12 | NP_001365707.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MPDZ | ENST00000319217.12 | c.2401G>T | p.Asp801Tyr | missense_variant | 18/47 | 5 | NM_001378778.1 | ENSP00000320006 | A1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 151870Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000801 AC: 17AN: 212242Hom.: 1 AF XY: 0.0000792 AC XY: 9AN XY: 113610
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GnomAD4 exome AF: 0.0000835 AC: 120AN: 1437040Hom.: 1 Cov.: 30 AF XY: 0.0000941 AC XY: 67AN XY: 712222
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GnomAD4 genome AF: 0.0000658 AC: 10AN: 151870Hom.: 0 Cov.: 32 AF XY: 0.0000405 AC XY: 3AN XY: 74140
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 29, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 801 of the MPDZ protein (p.Asp801Tyr). This variant is present in population databases (rs758473798, 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: 522684). 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. - |
Hydrocephalus, nonsyndromic, autosomal recessive 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Apr 27, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;.;.;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;D;D;D;.;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;M;M;M;M;.
MutationTaster
Benign
D;D;D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
0.98
.;D;D;.;D;.
Vest4
MVP
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at