1-84182237-C-A

Position:

• chr1-84182237-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1 PM2

The NM_182948.4(PRKACB):​c.287C>A​(p.Thr96Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PRKACB NM_182948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.91

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKACB	NM_182948.4	c.287C>A	p.Thr96Asn	missense_variant	3/10	ENST00000370685.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKACB	ENST00000370685.7	c.287C>A	p.Thr96Asn	missense_variant	3/10	1	NM_182948.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1441344 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 716722

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.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Benign	-0.039	T
BayesDel_noAF	Benign	-0.29
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T;.;.;.;.;.;.;.;T;.;.;.;.;.;.;.;T
Eigen	Uncertain	0.65
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.70	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-4.1	D;D;D;D;D;D;.;D;.;D;D;D;D;D;.;D;.
REVEL	Uncertain	0.38
Sift	Pathogenic	0.0	D;D;D;D;D;D;.;D;.;D;D;D;D;D;.;D;.
Sift4G	Uncertain	0.0050	D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D
Polyphen		0.97	D;P;D;.;.;.;D;P;.;.;.;P;.;.;D;.;.
Vest4		0.80
MutPred		0.63		Loss of phosphorylation at T49 (P = 0.0666);Loss of phosphorylation at T49 (P = 0.0666);.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;
MVP		0.51
MPC		2.1
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.88
gMVP		0.72

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: chr1-84647920;