chr9-13217184-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP3BP6
The NM_001378778.1(MPDZ):c.1197A>G(p.Lys399=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,573,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 0 hom. )
Consequence
MPDZ
NM_001378778.1 synonymous
NM_001378778.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.492
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;
PP3
?
Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
BP6
?
Variant 9-13217184-T-C is Benign according to our data. Variant chr9-13217184-T-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 211507.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPDZ | NM_001378778.1 | c.1197A>G | p.Lys399= | synonymous_variant | 9/47 | ENST00000319217.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPDZ | ENST00000319217.12 | c.1197A>G | p.Lys399= | synonymous_variant | 9/47 | 5 | NM_001378778.1 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000461 AC: 7AN: 151930Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000504 AC: 11AN: 218140Hom.: 0 AF XY: 0.0000680 AC XY: 8AN XY: 117688
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GnomAD4 exome AF: 0.000131 AC: 186AN: 1421390Hom.: 0 Cov.: 28 AF XY: 0.000118 AC XY: 83AN XY: 706364
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GnomAD4 genome ? AF: 0.0000461 AC: 7AN: 151930Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74208
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | May 21, 2015 | - - |
MPDZ-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 12, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at