Variant 1-84179234-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_182948.4(PRKACB):c.245C>T(p.Thr82Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000254 in 1,576,854 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

PRKACB
NM_182948.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.74

Variant links:

Genes affected

PRKACB (HGNC:9381): (protein kinase cAMP-activated catalytic subunit beta) The protein encoded by this gene is a member of the serine/threonine protein kinase family. The encoded protein is a catalytic subunit of cAMP (cyclic AMP)-dependent protein kinase, which mediates signalling though cAMP. cAMP signaling is important to a number of processes, including cell proliferaton and differentiation. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed. [provided by RefSeq, Jul 2014]

PRKACB links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a domain Protein kinase (size 254) in uniprot entity KAPCB_HUMAN there are 9 pathogenic changes around while only 1 benign (90%) in NM_182948.4

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15940094).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_182948.4 linkuse as main transcript	c.245C>T	p.Thr82Ile	missense_variant	2/10	ENST00000370685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370685.7 linkuse as main transcript	c.245C>T	p.Thr82Ile	missense_variant	2/10	1	NM_182948.4		P22694-2

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151702

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000211

AC:

AN:

1425152

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

707522

show subpopulations

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:

0.0000258

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.14e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151702

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74064

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Sep 02, 2022

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.14

Eigen_PC

Benign

0.044

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.016

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

0.99

N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.71

N;N;N;N;N;N;.;N;.;N;N;N;N;N;.;N

REVEL

Benign

0.063

Sift

Benign

0.081

T;T;T;T;T;T;.;T;.;D;T;T;T;T;.;T

Sift4G

Benign

0.13

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.021

B;B;B;.;.;.;B;B;.;.;.;B;.;.;B;.

Vest4

0.14

MutPred

0.30

Gain of catalytic residue at T35 (P = 0.007);Gain of catalytic residue at T35 (P = 0.007);.;.;.;.;.;.;.;.;.;.;.;.;.;.;

MVP

0.42

MPC

0.91

ClinPred

0.46

GERP RS

4.9

Varity_R

0.13

gMVP

0.32

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