NM_182948.4:c.83G>T

Variant names:

• chr1-84144444-G-T
• NM_182948.4:c.83G>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_182948.4(PRKACB):​c.83G>T​(p.Arg28Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R28Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: PRKACB NM_182948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.68

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.83G>T	p.Arg28Leu	missense_variant	Exon 1 of 10	ENST00000370685.7	NP_891993.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKACB	ENST00000370685.7	c.83G>T	p.Arg28Leu	missense_variant	Exon 1 of 10	1	NM_182948.4	ENSP00000359719.3
PRKACB	ENST00000370689.6	c.47-34733G>T		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.47-34733G>T		intron_variant	Intron 1 of 8	1		ENSP00000359722.3
PRKACB	ENST00000470673.5	n.123G>T		non_coding_transcript_exon_variant	Exon 1 of 7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460716 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 726718

Gnomad4 AFR exome AF: 0.0000300

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.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	25
DANN	Uncertain	1.0
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.047	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.59	T
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.080	N
REVEL	Benign	0.20
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.15	T
Polyphen		0.99	D
Vest4		0.87
MutPred		0.56		Loss of MoRF binding (P = 6e-04);
MVP		0.62
MPC		1.1
ClinPred		0.99	D
GERP RS		5.7
gMVP		0.48

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: chr1-84610127;