NM_000311.5:c.385A>G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_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 -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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PRNP | NM_000311.5 | c.385A>G | p.Met129Val | missense_variant | Exon 2 of 2 | ENST00000379440.9 | NP_000302.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRNP | ENST00000379440.9 | c.385A>G | p.Met129Val | missense_variant | Exon 2 of 2 | 1 | NM_000311.5 | ENSP00000368752.4 | ||
PRNP | ENST00000424424.2 | c.385A>G | p.Met129Val | missense_variant | Exon 2 of 2 | 1 | ENSP00000411599.2 | |||
PRNP | ENST00000430350.2 | c.385A>G | p.Met129Val | missense_variant | Exon 2 of 2 | 1 | ENSP00000399376.2 | |||
PRNP | ENST00000457586.2 | c.385A>G | p.Met129Val | missense_variant | Exon 2 of 2 | 1 | ENSP00000415284.2 |
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
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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:3
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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) -
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Huntington disease-like 1 Benign:2
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Autism spectrum disorder Uncertain:1
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
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Fatal familial insomnia Benign:1
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Inherited Creutzfeldt-Jakob disease Benign:1
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Inherited prion disease Benign:1
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
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ALZHEIMER DISEASE, EARLY-ONSET, SUSCEPTIBILITY TO Other:1
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APHASIA, PRIMARY PROGRESSIVE, SUSCEPTIBILITY TO Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at