Variant chr17-68531661-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002734.5(PRKAR1A):c.*1212T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,066,036 control chromosomes in the GnomAD database, including 8,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1271 hom., cov: 32)

Exomes 𝑓: 0.12 ( 6730 hom. )

Consequence

PRKAR1A
NM_002734.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.884

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 links:

PRKAR1A (HGNC:):

PRKAR1A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 17-68531661-T-G is Benign according to our data. Variant chr17-68531661-T-G is described in ClinVar as [Benign]. Clinvar id is 324806.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKAR1A	NM_002734.5 linkuse as main transcript	c.*1212T>G		3_prime_UTR_variant	11/11	ENST00000589228.6	NP_002725.1	P10644-1B2R5T5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKAR1A	ENST00000589228.6 linkuse as main transcript	c.*1212T>G		3_prime_UTR_variant	11/11	1	NM_002734.5	ENSP00000464977.2		P10644-1

Frequencies

GnomAD3 genomes

AF:

0.128

AC:

19410

AN:

152106

Hom.:

1269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.147

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.101

Gnomad EAS

AF:

0.104

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.136

GnomAD4 exome

AF:

0.121

AC:

110432

AN:

913812

Hom.:

6730

Cov.:

AF XY:

0.121

AC XY:

51079

AN XY:

421852

show subpopulations

Gnomad4 AFR exome

AF:

0.163

Gnomad4 AMR exome

AF:

0.0809

Gnomad4 ASJ exome

AF:

0.0999

Gnomad4 EAS exome

AF:

0.119

Gnomad4 SAS exome

AF:

0.0826

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.121

Gnomad4 OTH exome

AF:

0.116

GnomAD4 genome

AF:

0.128

AC:

19418

AN:

152224

Hom.:

1271

Cov.:

AF XY:

0.128

AC XY:

9527

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.146

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.101

Gnomad4 EAS

AF:

0.104

Gnomad4 SAS

AF:

0.0732

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.135

Alfa

AF:

0.106

Hom.:

759

Bravo

AF:

0.125

Asia WGS

AF:

0.0730

AC:

255

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Acrodysostosis

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Carney complex

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.85

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over