rs8315
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_014476.6(PDLIM3):c.*12C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0116 in 1,613,670 control chromosomes in the GnomAD database, including 164 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0093 ( 17 hom., cov: 33)
Exomes 𝑓: 0.012 ( 147 hom. )
Consequence
PDLIM3
NM_014476.6 3_prime_UTR
NM_014476.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.99
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 4-185502282-G-A is Benign according to our data. Variant chr4-185502282-G-A is described in ClinVar as [Benign]. Clinvar id is 138676.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-185502282-G-A is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0093 (1414/152124) while in subpopulation SAS AF= 0.0265 (128/4830). AF 95% confidence interval is 0.0228. There are 17 homozygotes in gnomad4. There are 666 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 17 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PDLIM3 | NM_014476.6 | c.*12C>T | 3_prime_UTR_variant | 8/8 | ENST00000284767.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM3 | ENST00000284767.12 | c.*12C>T | 3_prime_UTR_variant | 8/8 | 5 | NM_014476.6 | A1 | ||
ENST00000671042.1 | n.518-4219G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00930 AC: 1414AN: 152006Hom.: 17 Cov.: 33
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GnomAD3 exomes AF: 0.0111 AC: 2799AN: 251472Hom.: 30 AF XY: 0.0119 AC XY: 1621AN XY: 135912
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GnomAD4 exome AF: 0.0119 AC: 17351AN: 1461546Hom.: 147 Cov.: 30 AF XY: 0.0122 AC XY: 8891AN XY: 727108
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 04, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 20, 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 | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | *12C>T in exon 8 of PDLIM3: This variant is not expected to have clinical signif icance because it has been identified in 1.3% (111/8600) of European American ch romosomes from a broad population by the NHLBI Exome Sequencing Project (http:// evs.gs.washington.edu/EVS; dbSNP rs8315). - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at