chr7-550447-T-C

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001164760.2(PRKAR1B):ā€‹c.1129A>Gā€‹(p.Ile377Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

PRKAR1B
NM_001164760.2 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.62
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15201196).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKAR1BNM_001164760.2 linkuse as main transcriptc.1129A>G p.Ile377Val missense_variant 11/11 ENST00000537384.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKAR1BENST00000537384.6 linkuse as main transcriptc.1129A>G p.Ile377Val missense_variant 11/115 NM_001164760.2 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1441450
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
715070
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 02, 2023The c.1129A>G (p.I377V) alteration is located in exon 11 (coding exon 10) of the PRKAR1B gene. This alteration results from a A to G substitution at nucleotide position 1129, causing the isoleucine (I) at amino acid position 377 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.27
BayesDel_addAF
Benign
-0.0090
T
BayesDel_noAF
Benign
-0.25
CADD
Benign
17
DANN
Benign
0.80
DEOGEN2
Benign
0.082
T;T;T;T;T
Eigen
Benign
-0.51
Eigen_PC
Benign
-0.25
FATHMM_MKL
Uncertain
0.90
D
LIST_S2
Benign
0.83
T;.;.;.;.
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.15
T;T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
-0.34
N;N;N;N;N
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
0.38
N;N;N;N;N
REVEL
Uncertain
0.33
Sift
Benign
1.0
T;T;T;T;T
Sift4G
Benign
1.0
T;T;T;T;T
Polyphen
0.0
B;B;B;B;B
Vest4
0.18
MutPred
0.44
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.76
MPC
1.0
ClinPred
0.81
D
GERP RS
4.7
Varity_R
0.24
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-590084; API