rs62643364
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Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The ENST00000379440.9(PRNP):āc.246A>Gā(p.Gly82=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000937 in 1,569,202 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.00023 ( 0 hom., cov: 31)
Exomes š: 0.000081 ( 1 hom. )
Consequence
PRNP
ENST00000379440.9 synonymous
ENST00000379440.9 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -3.27
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=-0.92).
BP6
Variant 20-4699466-A-G is Benign according to our data. Variant chr20-4699466-A-G is described in ClinVar as [Benign]. Clinvar id is 338648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-3.27 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRNP | NM_000311.5 | c.246A>G | p.Gly82= | synonymous_variant | 2/2 | ENST00000379440.9 | NP_000302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRNP | ENST00000379440.9 | c.246A>G | p.Gly82= | synonymous_variant | 2/2 | 1 | NM_000311.5 | ENSP00000368752 | P1 | |
PRNP | ENST00000424424.2 | c.246A>G | p.Gly82= | synonymous_variant | 2/2 | 1 | ENSP00000411599 | P1 | ||
PRNP | ENST00000430350.2 | c.246A>G | p.Gly82= | synonymous_variant | 2/2 | 1 | ENSP00000399376 | P1 | ||
PRNP | ENST00000457586.2 | c.246A>G | p.Gly82= | synonymous_variant | 2/2 | 1 | ENSP00000415284 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000229 AC: 31AN: 135606Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000145 AC: 36AN: 248842Hom.: 1 AF XY: 0.000119 AC XY: 16AN XY: 134932
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GnomAD4 exome AF: 0.0000809 AC: 116AN: 1433514Hom.: 1 Cov.: 31 AF XY: 0.0000938 AC XY: 67AN XY: 714164
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GnomAD4 genome AF: 0.000228 AC: 31AN: 135688Hom.: 0 Cov.: 31 AF XY: 0.000210 AC XY: 14AN XY: 66556
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ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Inherited prion disease 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. - |
Huntington disease-like 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 21, 2020 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at