3-183842407-A-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1
The NM_018622.7(PARL):c.648T>C(p.His216=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 1,611,362 control chromosomes in the GnomAD database, including 183,246 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.47 ( 17230 hom., cov: 32)
Exomes 𝑓: 0.47 ( 166016 hom. )
Consequence
PARL
NM_018622.7 synonymous
NM_018622.7 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.16
Genes affected
PARL (HGNC:18253): (presenilin associated rhomboid like) This gene encodes a member of the rhomboid family of intramembrane serine proteases that is localized to the inner mitochondrial membrane. The encoded protein regulates mitochondrial remodeling and apoptosis through regulated substrate proteolysis. Proteolytic processing of the encoded protein results in the release of a small peptide, P-beta, which may transit to the nucleus. Mutations in this gene may be associated with Parkinson's disease. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP7
?
Synonymous conserved (PhyloP=1.16 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PARL | NM_018622.7 | c.648T>C | p.His216= | synonymous_variant | 6/10 | ENST00000317096.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PARL | ENST00000317096.9 | c.648T>C | p.His216= | synonymous_variant | 6/10 | 1 | NM_018622.7 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.473 AC: 71948AN: 151984Hom.: 17223 Cov.: 32
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GnomAD3 exomes AF: 0.468 AC: 117604AN: 251232Hom.: 28051 AF XY: 0.464 AC XY: 63063AN XY: 135802
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GnomAD4 exome AF: 0.475 AC: 692821AN: 1459260Hom.: 166016 Cov.: 33 AF XY: 0.474 AC XY: 343841AN XY: 726058
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GnomAD4 genome ? AF: 0.473 AC: 71971AN: 152102Hom.: 17230 Cov.: 32 AF XY: 0.466 AC XY: 34681AN XY: 74350
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ClinVar
Not reported inComputational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at