chr10-52290256-G-A
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2
The NM_006258.4(PRKG1):c.1928G>A(p.Arg643Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000158 in 1,612,910 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). Synonymous variant affecting the same amino acid position (i.e. R643R) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1928G>A | p.Arg643Lys | missense_variant | 17/18 | ENST00000373980.11 | |
PRKG1 | NM_001098512.3 | c.1883G>A | p.Arg628Lys | missense_variant | 17/18 | ||
PRKG1 | NM_001374781.1 | c.719G>A | p.Arg240Lys | missense_variant | 13/14 | ||
PRKG1 | XM_017016413.2 | c.1625G>A | p.Arg542Lys | missense_variant | 17/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1928G>A | p.Arg643Lys | missense_variant | 17/18 | 1 | NM_006258.4 | ||
PRKG1-AS1 | ENST00000452247.7 | n.461+3659C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 152082Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000359 AC: 9AN: 250856Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135580
GnomAD4 exome AF: 0.000168 AC: 246AN: 1460828Hom.: 0 Cov.: 30 AF XY: 0.000168 AC XY: 122AN XY: 726744
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152082Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74284
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 14, 2023 | - - |
PRKG1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 15, 2024 | The PRKG1 c.1928G>A variant is predicted to result in the amino acid substitution p.Arg643Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0070% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Aortic aneurysm, familial thoracic 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 07, 2023 | This variant has not been reported in the literature in individuals affected with PRKG1-related conditions. 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. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 520133). This variant is present in population databases (rs770812712, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 643 of the PRKG1 protein (p.Arg643Lys). - |
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 12, 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at