chr17-68524064-T-C
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_002734.5(PRKAR1A):āc.489T>Cā(p.Thr163=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Synonymous variant affecting the same amino acid position (i.e. T163T) has been classified as Likely benign.
Frequency
Consequence
NM_002734.5 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKAR1A | NM_002734.5 | c.489T>C | p.Thr163= | synonymous_variant | 5/11 | ENST00000589228.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKAR1A | ENST00000589228.6 | c.489T>C | p.Thr163= | synonymous_variant | 5/11 | 1 | NM_002734.5 | P1 | |
ENST00000590353.1 | n.668T>C | non_coding_transcript_exon_variant | 5/6 | 4 |
Frequencies
GnomAD3 genomes AF: 0.000854 AC: 130AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000211 AC: 53AN: 251422Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135876
GnomAD4 exome AF: 0.0000698 AC: 102AN: 1461774Hom.: 0 Cov.: 31 AF XY: 0.0000454 AC XY: 33AN XY: 727192
GnomAD4 genome AF: 0.000853 AC: 130AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.000805 AC XY: 60AN XY: 74492
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Feb 01, 2019 | Variant summary: PRKAR1A c.489T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00031 in 282814 control chromosomes in the gnomAD database, predominantly within the African subpopulation at a frequency of 0.0034. The observed variant frequency within African control individuals in the gnomAD database is approximately 1800 fold of the estimated maximal expected allele frequency for a pathogenic variant in PRKAR1A causing Carney Complex phenotype (1.9e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.489T>C in individuals affected with Carney Complex and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 28, 2022 | - - |
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | PRKAR1A: BP4, BP7, BS1 - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2017 | 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. - |
Benign, criteria provided, single submitter | curation | Sema4, Sema4 | Oct 22, 2020 | - - |
Familial atrial myxoma Benign:1
Benign, criteria provided, single submitter | clinical testing | KCCC/NGS Laboratory, Kuwait Cancer Control Center | Jul 07, 2023 | - - |
Carney complex, type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
PRKAR1A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 20, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at