NM_002734.5:c.709-341T>C

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002734.5(PRKAR1A):c.709-341T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 271,514 control chromosomes in the GnomAD database, including 6,846 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 3919 hom., cov: 32)

Exomes 𝑓: 0.21 ( 2927 hom. )

Consequence

PRKAR1A
NM_002734.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.308

Publications

7 publications found

Variant links:

Genes affected

PRKAR1A (HGNC:9388): (protein kinase cAMP-dependent type I regulatory subunit alpha) cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the cAMP-dependent protein kinase, which transduces the signal through phosphorylation of different target proteins. The inactive kinase holoenzyme is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits have been identified in humans. This gene encodes one of the regulatory subunits. This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids. Mutations in this gene cause Carney complex (CNC). This gene can fuse to the RET protooncogene by gene rearrangement and form the thyroid tumor-specific chimeric oncogene known as PTC2. A nonconventional nuclear localization sequence (NLS) has been found for this protein which suggests a role in DNA replication via the protein serving as a nuclear transport protein for the second subunit of the Replication Factor C (RFC40). Several alternatively spliced transcript variants encoding two different isoforms have been observed. [provided by RefSeq, Jan 2013]

PRKAR1A Gene-Disease associations (from GenCC):

Acrodysostosis 1 with or without hormone resistance
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
acrodysostosis with multiple hormone resistance
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
Carney complex, type 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
pigmented nodular adrenocortical disease, primary, 1
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, Ambry Genetics
acrodysostosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Carney complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial atrial myxoma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
primary pigmented nodular adrenocortical disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PRKAR1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002734.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKAR1A	NM_002734.5	MANE Select	c.709-341T>C	intron	N/A	NP_002725.1	B2R5T5
PRKAR1A	NM_001276289.2		c.709-341T>C	intron	N/A	NP_001263218.1	P10644-1
PRKAR1A	NM_001278433.2		c.709-341T>C	intron	N/A	NP_001265362.1	B2R5T5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRKAR1A	ENST00000589228.6	TSL:1 MANE Select	c.709-341T>C	intron	N/A	ENSP00000464977.2	P10644-1
PRKAR1A	ENST00000358598.6	TSL:1	c.709-341T>C	intron	N/A	ENSP00000351410.1	P10644-1
PRKAR1A	ENST00000536854.6	TSL:1	c.709-341T>C	intron	N/A	ENSP00000445625.1	P10644-1

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34292

AN:

151956

Hom.:

3921

Cov.:

show subpopulations

Gnomad AFR

AF:

0.239

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.198

Gnomad EAS

AF:

0.171

Gnomad SAS

AF:

0.259

Gnomad FIN

AF:

0.266

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.228

Gnomad OTH

AF:

0.215

GnomAD4 exome

AF:

0.214

AC:

25548

AN:

119440

Hom.:

2927

AF XY:

0.218

AC XY:

14146

AN XY:

64948

show subpopulations

African (AFR)

AF:

0.221

AC:

612

AN:

2772

American (AMR)

AF:

0.162

AC:

767

AN:

4742

Ashkenazi Jewish (ASJ)

AF:

0.182

AC:

529

AN:

2912

East Asian (EAS)

AF:

0.179

AC:

993

AN:

5556

South Asian (SAS)

AF:

0.251

AC:

5374

AN:

21398

European-Finnish (FIN)

AF:

0.240

AC:

1199

AN:

4990

Middle Eastern (MID)

AF:

0.266

AC:

111

AN:

418

European-Non Finnish (NFE)

AF:

0.208

AC:

14658

AN:

70628

Other (OTH)

AF:

0.217

AC:

1305

AN:

6024

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

927

1854

2780

3707

4634

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.226

AC:

34302

AN:

152074

Hom.:

3919

Cov.:

AF XY:

0.226

AC XY:

16777

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.239

AC:

9912

AN:

41474

American (AMR)

AF:

0.173

AC:

2648

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.198

AC:

686

AN:

3466

East Asian (EAS)

AF:

0.169

AC:

877

AN:

5176

South Asian (SAS)

AF:

0.260

AC:

1257

AN:

4828

European-Finnish (FIN)

AF:

0.266

AC:

2809

AN:

10564

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.228

AC:

15487

AN:

67980

Other (OTH)

AF:

0.213

AC:

450

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1359

2719

4078

5438

6797

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

380

760

1140

1520

1900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.222

Hom.:

689

Bravo

AF:

0.218

Asia WGS

AF:

0.211

AC:

734

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.5

(source)

DANN

Benign

0.73

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over