Variant 1-84144481-T-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182948.4(PRKACB):c.120T>A(p.Asp40Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,459,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D40N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PRKACB
NM_182948.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0270

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07497594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACB	NM_182948.4 link	c.120T>A	p.Asp40Glu	missense_variant	1/10	ENST00000370685.7	NP_891993.1	P22694-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRKACB	ENST00000370685.7 link	c.120T>A	p.Asp40Glu	missense_variant	1/10	1	NM_182948.4	ENSP00000359719.3	P22694-2
PRKACB	ENST00000370689.6 link	c.47-34696T>A		intron_variant		1		ENSP00000359723.2	P22694-1
PRKACB	ENST00000370688.7 link	c.47-34696T>A		intron_variant		1		ENSP00000359722.3	P22694-8
PRKACB	ENST00000470673.5 link	n.160T>A		non_coding_transcript_exon_variant	1/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459796

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726250

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:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 10, 2024

The c.120T>A (p.D40E) alteration is located in exon 1 (coding exon 1) of the PRKACB gene. This alteration results from a T to A substitution at nucleotide position 120, causing the aspartic acid (D) at amino acid position 40 to be replaced by a glutamic acid (E). 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

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.53

M_CAP

Benign

0.0047

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.43

PROVEAN

Benign

0.23

REVEL

Benign

0.11

Sift

Benign

0.60

Sift4G

Benign

0.59

Polyphen

0.0

Vest4

0.20

MutPred

0.14

Gain of methylation at K35 (P = 0.1132);

MVP

0.30

MPC

0.79

ClinPred

0.88

GERP RS

3.2

gMVP

0.19

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over