rs199725025
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003690.5(PRKRA):c.851G>T(p.Cys284Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000421 in 1,614,218 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., cov: 35)
Exomes 𝑓: 0.000041 ( 0 hom. )
Consequence
PRKRA
NM_003690.5 missense
NM_003690.5 missense
Scores
10
8
1
Clinical Significance
Conservation
PhyloP100: 6.88
Genes affected
PRKRA (HGNC:9438): (protein activator of interferon induced protein kinase EIF2AK2) This gene encodes a protein kinase activated by double-stranded RNA which mediates the effects of interferon in response to viral infection. Mutations in this gene have been associated with dystonia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.917
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKRA | NM_003690.5 | c.851G>T | p.Cys284Phe | missense_variant | 8/8 | ENST00000325748.9 | |
CHROMR | NR_110204.1 | n.872-1194C>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKRA | ENST00000325748.9 | c.851G>T | p.Cys284Phe | missense_variant | 8/8 | 1 | NM_003690.5 | P1 | |
CHROMR | ENST00000453026.7 | n.896-1194C>A | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000525 AC: 8AN: 152238Hom.: 0 Cov.: 35
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251364Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135874
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GnomAD4 exome AF: 0.0000410 AC: 60AN: 1461862Hom.: 0 Cov.: 60 AF XY: 0.0000371 AC XY: 27AN XY: 727236
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GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152356Hom.: 0 Cov.: 35 AF XY: 0.0000537 AC XY: 4AN XY: 74502
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Dystonia 16 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Uncertain
D;.;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;.;P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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