rs761759814
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_006258.4(PRKG1):āc.421A>Cā(p.Lys141Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,612,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K141E) has been classified as Uncertain significance.
Frequency
Consequence
NM_006258.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.421A>C | p.Lys141Gln | missense_variant | 2/18 | ENST00000373980.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.421A>C | p.Lys141Gln | missense_variant | 2/18 | 1 | NM_006258.4 |
Frequencies
GnomAD3 genomes AF: 0.0000461 AC: 7AN: 151984Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.000108 AC: 27AN: 250762Hom.: 0 AF XY: 0.0000885 AC XY: 12AN XY: 135524
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1460372Hom.: 0 Cov.: 30 AF XY: 0.0000179 AC XY: 13AN XY: 726510
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152100Hom.: 0 Cov.: 31 AF XY: 0.0000538 AC XY: 4AN XY: 74350
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 8 Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 09, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 19, 2023 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 27, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at