20-4699605-A-G
Variant summary
Our verdict is Benign. Variant got -18 ACMG points: 2P and 20B. PM1BP4_StrongBP6_Very_StrongBA1
The NM_000311.5(PRNP):āc.385A>Gā(p.Met129Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 1,613,794 control chromosomes in the GnomAD database, including 89,542 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Consequence
NM_000311.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRNP | NM_000311.5 | c.385A>G | p.Met129Val | missense_variant | 2/2 | ENST00000379440.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRNP | ENST00000379440.9 | c.385A>G | p.Met129Val | missense_variant | 2/2 | 1 | NM_000311.5 | P1 | |
PRNP | ENST00000424424.2 | c.385A>G | p.Met129Val | missense_variant | 2/2 | 1 | P1 | ||
PRNP | ENST00000430350.2 | c.385A>G | p.Met129Val | missense_variant | 2/2 | 1 | P1 | ||
PRNP | ENST00000457586.2 | c.385A>G | p.Met129Val | missense_variant | 2/2 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.329 AC: 49966AN: 151820Hom.: 8501 Cov.: 31
GnomAD3 exomes AF: 0.309 AC: 77663AN: 251266Hom.: 13110 AF XY: 0.305 AC XY: 41416AN XY: 135834
GnomAD4 exome AF: 0.328 AC: 479223AN: 1461854Hom.: 81027 Cov.: 71 AF XY: 0.325 AC XY: 236250AN XY: 727218
GnomAD4 genome ? AF: 0.329 AC: 50030AN: 151940Hom.: 8515 Cov.: 31 AF XY: 0.327 AC XY: 24291AN XY: 74278
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 03, 2018 | This variant is associated with the following publications: (PMID: 23399523, 20711061, 12601712, 10360778, 10079068, 23405858, 22669942, 23209282, 24249784, 16897605, 11684342, 22912570, 12660994, 2783132, 26061765, 27910931, 30917570, 31182772, 24340298, 30817871, 19081515, 24620982, 32949544, 8105681) - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Nov 29, 2023 | - - |
Huntington disease-like 1 Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Autism spectrum disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Gene Friend Way, National Innovation Center | Jul 28, 2023 | Results in an increased risk of prion disease and long term memory issues (PMID 1677164, PMID 15987701). This gene encodes a protein that is active in the brain and other tissues. In our study, about 10% of patients diagnosed with Autism Spectrum Disorder carry this variant. However, due to high frequency of the variant in the Vietnamese population, the pathogenicity of this variant is uncertain. - |
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
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 22, 2021 | - - |
Fatal familial insomnia Benign:1
Benign, criteria provided, single submitter | not provided | Institute of Human Genetics, University Hospital of Duesseldorf | - | - - |
Inherited Creutzfeldt-Jakob disease Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | Jan 01, 2019 | - - |
Inherited prion disease Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. - |
PRION DISEASE, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 19, 2009 | - - |
ALZHEIMER DISEASE, EARLY-ONSET, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 19, 2009 | - - |
APHASIA, PRIMARY PROGRESSIVE, SUSCEPTIBILITY TO Other:1
risk factor, no assertion criteria provided | literature only | OMIM | Nov 19, 2009 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at