rs989145213

Variant names:

• chr1-84144525-A-C
• rs989145213
• NM_182948.4:c.164A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-84144525-A-C
• chr1-84144525-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182948.4(PRKACB):​c.164A>C​(p.His55Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,344 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign 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. H55R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRKACB NM_182948.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19540974).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKACB	NM_182948.4	c.164A>C	p.His55Pro	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.164A>C	p.His55Pro	missense_variant	Exon 1 of 10	1	NM_182948.4	ENSP00000359719.3
PRKACB	ENST00000370689.6	c.47-34652A>C		intron_variant	Intron 1 of 9	1		ENSP00000359723.2
PRKACB	ENST00000370688.7	c.47-34652A>C		intron_variant	Intron 1 of 8	1		ENSP00000359722.3
PRKACB	ENST00000470673.5	n.204A>C		non_coding_transcript_exon_variant	Exon 1 of 7	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000206 AC: 3 AN: 1456344 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724536

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: 0.00000270

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	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Benign	0.92
Eigen	Benign	-0.22
Eigen_PC	Benign	0.0024
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.46	T
PROVEAN	Benign	0.050	N
REVEL	Benign	0.074
Sift	Benign	0.20	T
Sift4G	Benign	0.19	T
Polyphen		0.0	B
Vest4		0.46
MutPred		0.33		Gain of glycosylation at S53 (P = 0.1517);
MVP		0.54
MPC		1.3
ClinPred		0.62	D
GERP RS		5.6
gMVP		0.68

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

Other links and lift over

dbSNP: rs989145213; hg19: chr1-84610208;