NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=) AND not specified

Clinical significance:Benign/Likely benign (Last evaluated: Feb 1, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=)]

NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=)

PRKAR1A:protein kinase cAMP-dependent type I regulatory subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=)
  • NC_000017.11:g.68524064T>C
  • NG_007093.3:g.115442T>C
  • NM_001276289.1:c.489T>C
  • NM_001276290.1:c.489T>C
  • NM_001278433.1:c.489T>C
  • NM_001369389.1:c.489T>C
  • NM_001369390.1:c.489T>C
  • NM_002734.4:c.489T>C
  • NM_212471.2:c.489T>C
  • NM_212472.2:c.489T>C
  • NP_001263218.1:p.Thr163=
  • NP_001263219.1:p.Thr163=
  • NP_001265362.1:p.Thr163=
  • NP_001356318.1:p.Thr163=
  • NP_001356319.1:p.Thr163=
  • NP_002725.1:p.Thr163=
  • NP_997636.1:p.Thr163=
  • NP_997637.1:p.Thr163=
  • LRG_514t1:c.489T>C
  • LRG_514t2:c.489T>C
  • LRG_514:g.115442T>C
  • LRG_514p1:p.Thr163=
  • LRG_514p2:p.Thr163=
  • NC_000017.10:g.66520205T>C
  • NM_002734.3:c.489T>C
dbSNP: rs143672551
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001276289.1:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001276290.1:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001278433.1:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369389.1:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_001369390.1:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_002734.4:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_212471.2:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]
  • NM_212472.2:c.489T>C - synonymous variant - [Sequence Ontology: SO:0001819]


MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000715739GeneDxcriteria provided, single submitter
Likely benign
(Feb 6, 2017)
germlineclinical testing

Citation Link,

SCV001362691Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
(Feb 1, 2019)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000715739.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362691.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


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.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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