rs112661328
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_014476.6(PDLIM3):c.162C>T(p.Gly54=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00994 in 1,614,126 control chromosomes in the GnomAD database, including 106 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0071 ( 7 hom., cov: 33)
Exomes 𝑓: 0.010 ( 99 hom. )
Consequence
PDLIM3
NM_014476.6 synonymous
NM_014476.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.74
Genes affected
PDLIM3 (HGNC:20767): (PDZ and LIM domain 3) The protein encoded by this gene contains a PDZ domain and a LIM domain, indicating that it may be involved in cytoskeletal assembly. In support of this, the encoded protein has been shown to bind the spectrin-like repeats of alpha-actinin-2 and to colocalize with alpha-actinin-2 at the Z lines of skeletal muscle. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. Aberrant alternative splicing of this gene may play a role in myotonic dystrophy. [provided by RefSeq, Apr 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.32).
BP6
?
Variant 4-185525103-G-A is Benign according to our data. Variant chr4-185525103-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 138668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-185525103-G-A is described in Lovd as [Benign]. Variant chr4-185525103-G-A is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=1.74 with no splicing effect.
BS2
?
High Homozygotes in GnomAd4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM3 | NM_014476.6 | c.162C>T | p.Gly54= | synonymous_variant | 2/8 | ENST00000284767.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM3 | ENST00000284767.12 | c.162C>T | p.Gly54= | synonymous_variant | 2/8 | 5 | NM_014476.6 | A1 |
Frequencies
GnomAD3 genomes ? AF: 0.00707 AC: 1076AN: 152204Hom.: 7 Cov.: 33
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GnomAD3 exomes AF: 0.00799 AC: 2008AN: 251356Hom.: 18 AF XY: 0.00783 AC XY: 1064AN XY: 135846
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GnomAD4 exome AF: 0.0102 AC: 14971AN: 1461804Hom.: 99 Cov.: 31 AF XY: 0.00986 AC XY: 7167AN XY: 727212
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GnomAD4 genome ? AF: 0.00707 AC: 1077AN: 152322Hom.: 7 Cov.: 33 AF XY: 0.00709 AC XY: 528AN XY: 74488
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:6
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 11, 2014 | 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. - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 26, 2023 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Gly54Gly in exon 2 of PDLIM3: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 1.0% (85/8600) of Eu ropean American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs112661328). - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2022 | 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. - |
Primary dilated cardiomyopathy;C0007194:Hypertrophic cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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