chr7-550434-A-C

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001164760.2(PRKAR1B):​c.1142T>G​(p.Val381Gly) 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 (★).

Frequency

Genomes: not found (cov: 33)

Consequence

PRKAR1B
NM_001164760.2 missense

Scores

11
6
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.66
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.82

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PRKAR1BNM_001164760.2 linkuse as main transcriptc.1142T>G p.Val381Gly missense_variant 11/11 ENST00000537384.6 NP_001158232.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PRKAR1BENST00000537384.6 linkuse as main transcriptc.1142T>G p.Val381Gly missense_variant 11/115 NM_001164760.2 ENSP00000440449 P1

Frequencies

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

ClinVar

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

Submissions by phenotype

Marbach-Schaaf neurodevelopmental syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testing3billionMar 22, 2022The variant is not observed in the gnomAD v2.1.1 dataset. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.734>=0.6, 3CNET: 0.996>=0.75). A missense variant is a common mechanism . Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Pathogenic
0.45
D
BayesDel_noAF
Pathogenic
0.40
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.58
D;D;D;D;D
Eigen
Pathogenic
0.71
Eigen_PC
Uncertain
0.65
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.76
T;.;.;.;.
M_CAP
Pathogenic
0.42
D
MetaRNN
Pathogenic
0.82
D;D;D;D;D
MetaSVM
Uncertain
0.36
D
MutationAssessor
Uncertain
2.6
M;M;M;M;M
MutationTaster
Benign
1.0
D;D;D;D;D
PrimateAI
Pathogenic
0.80
T
PROVEAN
Uncertain
-3.3
D;D;D;D;D
REVEL
Pathogenic
0.73
Sift
Pathogenic
0.0
D;D;D;D;D
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
D;D;D;D;D
Vest4
0.71
MutPred
0.38
Loss of stability (P = 3e-04);Loss of stability (P = 3e-04);Loss of stability (P = 3e-04);Loss of stability (P = 3e-04);Loss of stability (P = 3e-04);
MVP
0.95
MPC
1.4
ClinPred
0.97
D
GERP RS
4.7
Varity_R
0.61
gMVP
0.83

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: chr7-590071; API