rs775720873
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_006258.4(PRKG1):āc.1016T>Cā(p.Leu339Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000236 in 1,612,640 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 (ā ). Synonymous variant affecting the same amino acid position (i.e. L339L) has been classified as Likely benign.
Frequency
Consequence
NM_006258.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1016T>C | p.Leu339Ser | missense_variant | 9/18 | ENST00000373980.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1016T>C | p.Leu339Ser | missense_variant | 9/18 | 1 | NM_006258.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 250632Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135478
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1460548Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 726590
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74286
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Aortic aneurysm, familial thoracic 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 13, 2023 | This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 339 of the PRKG1 protein (p.Leu339Ser). This variant is present in population databases (rs775720873, gnomAD 0.005%). This missense change has been observed in individuals with PRKG1-related conditions (PMID: 29907982; Invitae). This variant is also known as c.971T>C (p.Leu324Ser). ClinVar contains an entry for this variant (Variation ID: 544055). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at