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:
current
Accession:
RCV000601259.2

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

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

Gene:
PRKAR1A:protein kinase cAMP-dependent type I regulatory subunit alpha [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q24.2
Genomic location:
Preferred name:
NM_212472.2(PRKAR1A):c.489T>C (p.Thr163=)
HGVS:
  • 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
Links:
dbSNP: rs143672551
NCBI 1000 Genomes Browser:
rs143672551
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]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
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
Benign
(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

Description

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.

#SampleMethodObservation
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

Description

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.

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

Last Updated: Jun 14, 2021

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