20-4699379-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_000311.5(PRNP):c.159C>T(p.Gly53=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000508 in 1,613,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
PRNP
NM_000311.5 synonymous
NM_000311.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.33
Genes affected
PRNP (HGNC:9449): (prion protein (Kanno blood group)) The protein encoded by this gene is a membrane glycosylphosphatidylinositol-anchored glycoprotein that tends to aggregate into rod-like structures. The encoded protein contains a highly unstable region of five tandem octapeptide repeats. This gene is found on chromosome 20, approximately 20 kbp upstream of a gene which encodes a biochemically and structurally similar protein to the one encoded by this gene. Mutations in the repeat region as well as elsewhere in this gene have been associated with Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Straussler disease, Huntington disease-like 1, and kuru. An overlapping open reading frame has been found for this gene that encodes a smaller, structurally unrelated protein, AltPrp. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]
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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=-0.67).
BP6
?
Variant 20-4699379-C-T is Benign according to our data. Variant chr20-4699379-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 338645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr20-4699379-C-T is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-2.33 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRNP | NM_000311.5 | c.159C>T | p.Gly53= | synonymous_variant | 2/2 | ENST00000379440.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRNP | ENST00000379440.9 | c.159C>T | p.Gly53= | synonymous_variant | 2/2 | 1 | NM_000311.5 | P1 | |
PRNP | ENST00000424424.2 | c.159C>T | p.Gly53= | synonymous_variant | 2/2 | 1 | P1 | ||
PRNP | ENST00000430350.2 | c.159C>T | p.Gly53= | synonymous_variant | 2/2 | 1 | P1 | ||
PRNP | ENST00000457586.2 | c.159C>T | p.Gly53= | synonymous_variant | 2/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000462 AC: 7AN: 151572Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000524 AC: 13AN: 248054Hom.: 0 AF XY: 0.0000889 AC XY: 12AN XY: 134918
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GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461484Hom.: 0 Cov.: 31 AF XY: 0.0000619 AC XY: 45AN XY: 727070
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Gerstmann-Straussler-Scheinker syndrome;C0206042:Fatal familial insomnia;C0751254:Inherited Creutzfeldt-Jakob disease;C1847650:Spongiform encephalopathy with neuropsychiatric features;C1855588:Kuru, susceptibility to;C1864112:Huntington disease-like 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 20, 2021 | - - |
Inherited prion disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 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. - |
Huntington disease-like 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | May 09, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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