2-178451030-T-G
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001316362.2(PRKRA):c.-449A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,336,412 control chromosomes in the GnomAD database, including 6,399 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001316362.2 5_prime_UTR_premature_start_codon_gain
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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PRKRA | NM_003690.5 | c.1A>C | p.Met1? | initiator_codon_variant | Exon 1 of 8 | ENST00000325748.9 | NP_003681.1 | |
PRKRA | NM_001316362.2 | c.-449A>C | 5_prime_UTR_premature_start_codon_gain_variant | Exon 1 of 9 | NP_001303291.1 | |||
PRKRA | XM_047446138.1 | c.1A>C | p.Met1? | initiator_codon_variant | Exon 1 of 6 | XP_047302094.1 | ||
PRKRA | NM_001316362.2 | c.-449A>C | 5_prime_UTR_variant | Exon 1 of 9 | NP_001303291.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0474 AC: 5848AN: 123394Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.257 AC: 41222AN: 160416Hom.: 6543 AF XY: 0.255 AC XY: 22426AN XY: 87862
GnomAD4 exome AF: 0.134 AC: 162052AN: 1212914Hom.: 6399 Cov.: 38 AF XY: 0.134 AC XY: 80350AN XY: 601090
GnomAD4 genome AF: 0.0474 AC: 5851AN: 123498Hom.: 0 Cov.: 34 AF XY: 0.0461 AC XY: 2786AN XY: 60438
ClinVar
Submissions by phenotype
Dystonia 16 Benign:3
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. -
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not provided Benign:2
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not specified Benign:1
Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency in 1000Genomes: 354/2178=16.25% -
Hearing loss, autosomal recessive Benign:1
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Dystonic disorder Benign:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at