chr4-185502205-T-C
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_014476.6(PDLIM3):c.*89A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,329,556 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.010 ( 17 hom., cov: 33)
Exomes 𝑓: 0.012 ( 127 hom. )
Consequence
PDLIM3
NM_014476.6 3_prime_UTR
NM_014476.6 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.616
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 -14 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
?
Variant 4-185502205-T-C is Benign according to our data. Variant chr4-185502205-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 1318143.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00996 (1517/152360) while in subpopulation SAS AF= 0.0265 (128/4832). AF 95% confidence interval is 0.0228. There are 17 homozygotes in gnomad4. There are 718 alleles in male gnomad4 subpopulation. Median coverage is 33. 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.*89A>G | 3_prime_UTR_variant | 8/8 | ENST00000284767.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PDLIM3 | ENST00000284767.12 | c.*89A>G | 3_prime_UTR_variant | 8/8 | 5 | NM_014476.6 | A1 | ||
ENST00000671042.1 | n.518-4296T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.00996 AC: 1516AN: 152242Hom.: 17 Cov.: 33
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GnomAD4 exome AF: 0.0117 AC: 13830AN: 1177196Hom.: 127 Cov.: 17 AF XY: 0.0121 AC XY: 7279AN XY: 599198
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GnomAD4 genome ? AF: 0.00996 AC: 1517AN: 152360Hom.: 17 Cov.: 33 AF XY: 0.00964 AC XY: 718AN XY: 74512
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 16, 2018 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at