rs200354645
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6BP7
The NM_014476.6(PDLIM3):c.246G>A(p.Arg82=) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000164 in 1,586,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_014476.6 splice_region, synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM3 | NM_014476.6 | c.246G>A | p.Arg82= | splice_region_variant, synonymous_variant | 3/8 | ENST00000284767.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM3 | ENST00000284767.12 | c.246G>A | p.Arg82= | splice_region_variant, synonymous_variant | 3/8 | 5 | NM_014476.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.000145 AC: 22AN: 152152Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000261 AC: 65AN: 248824Hom.: 0 AF XY: 0.000312 AC XY: 42AN XY: 134490
GnomAD4 exome AF: 0.000167 AC: 239AN: 1434516Hom.: 1 Cov.: 25 AF XY: 0.000180 AC XY: 129AN XY: 715190
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.000107 AC XY: 8AN XY: 74446
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 14, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 07, 2017 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:2
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 10, 2023 | This sequence change affects codon 82 of the PDLIM3 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PDLIM3 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200354645, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with PDLIM3-related conditions. ClinVar contains an entry for this variant (Variation ID: 380756). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at