10-52280851-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_006258.4(PRKG1):āc.1466A>Gā(p.Tyr489Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,214 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 ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y489F) 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_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1466A>G | p.Tyr489Cys | missense_variant | 13/18 | ENST00000373980.11 | |
PRKG1 | NM_001098512.3 | c.1421A>G | p.Tyr474Cys | missense_variant | 13/18 | ||
PRKG1 | NM_001374781.1 | c.257A>G | p.Tyr86Cys | missense_variant | 9/14 | ||
PRKG1 | XM_017016413.2 | c.1163A>G | p.Tyr388Cys | missense_variant | 13/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1466A>G | p.Tyr489Cys | missense_variant | 13/18 | 1 | NM_006258.4 | ||
PRKG1-AS1 | ENST00000452247.7 | n.461+13064T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250544Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135378
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461214Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726946
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 8 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2021 | This variant has not been reported in the literature in individuals affected with PRKG1-related conditions. This variant is present in population databases (rs149710600, gnomAD 0.0009%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 489 of the PRKG1 protein (p.Tyr489Cys). ClinVar contains an entry for this variant (Variation ID: 407089). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at