rs1057519490

Positions:

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001164760.2(PRKAR1B):​c.149T>G​(p.Leu50Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 33)

Consequence

PRKAR1B
NM_001164760.2 missense

Scores

5
13
1

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 8.61
Variant links:
Genes affected
PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.888

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKAR1BNM_001164760.2 linkuse as main transcriptc.149T>G p.Leu50Arg missense_variant 2/11 ENST00000537384.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAR1BENST00000537384.6 linkuse as main transcriptc.149T>G p.Leu50Arg missense_variant 2/115 NM_001164760.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, no assertion criteria providedliterature onlyOMIMDec 23, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.99
BayesDel_addAF
Pathogenic
0.24
D
BayesDel_noAF
Uncertain
0.10
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.66
D;D;D;D;D;T;.;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D;.;.;.;.;D;D;D
M_CAP
Pathogenic
0.67
D
MetaRNN
Pathogenic
0.89
D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.40
D
MutationAssessor
Uncertain
2.5
M;M;M;M;M;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Uncertain
-3.5
D;D;D;D;D;D;D;D
REVEL
Pathogenic
0.90
Sift
Uncertain
0.0010
D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.043
D;D;D;D;D;D;.;D
Polyphen
0.96
D;D;D;D;D;.;.;.
Vest4
0.88
MutPred
0.65
Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);Loss of stability (P = 0.0465);
MVP
0.94
MPC
1.4
ClinPred
0.99
D
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.83
gMVP
0.82

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.

Other links and lift over

dbSNP: rs1057519490; hg19: chr7-750994; API