chr6-162443370-C-T
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_004562.3(PRKN):c.111G>A(p.Pro37=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00594 in 1,613,604 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.031 ( 266 hom., cov: 32)
Exomes 𝑓: 0.0034 ( 231 hom. )
Consequence
PRKN
NM_004562.3 synonymous
NM_004562.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.116
Genes affected
PRKN (HGNC:8607): (parkin RBR E3 ubiquitin protein ligase) The precise function of this gene is unknown; however, the encoded protein is a component of a multiprotein E3 ubiquitin ligase complex that mediates the targeting of substrate proteins for proteasomal degradation. Mutations in this gene are known to cause Parkinson disease and autosomal recessive juvenile Parkinson disease. Alternative splicing of this gene produces multiple transcript variants encoding distinct isoforms. Additional splice variants of this gene have been described but currently lack transcript support. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.47).
BP6
Variant 6-162443370-C-T is Benign according to our data. Variant chr6-162443370-C-T is described in ClinVar as [Benign]. Clinvar id is 356020.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.116 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKN | NM_004562.3 | c.111G>A | p.Pro37= | synonymous_variant | 2/12 | ENST00000366898.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKN | ENST00000366898.6 | c.111G>A | p.Pro37= | synonymous_variant | 2/12 | 1 | NM_004562.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0308 AC: 4684AN: 152046Hom.: 266 Cov.: 32
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GnomAD3 exomes AF: 0.00838 AC: 2107AN: 251364Hom.: 103 AF XY: 0.00619 AC XY: 841AN XY: 135844
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GnomAD4 exome AF: 0.00335 AC: 4902AN: 1461440Hom.: 231 Cov.: 33 AF XY: 0.00300 AC XY: 2183AN XY: 727030
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GnomAD4 genome AF: 0.0308 AC: 4690AN: 152164Hom.: 266 Cov.: 32 AF XY: 0.0300 AC XY: 2235AN XY: 74386
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2018 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Apr 22, 2021 | - - |
Autosomal recessive juvenile Parkinson disease 2 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
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