chr7-551445-C-A

Variant names:

• chr7-551445-C-A
• rs866622752
• NM_001164760.2:c.917G>T

Variant summary

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

The NM_001164760.2(PRKAR1B):​c.917G>T​(p.Arg306Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000213 in 1,406,502 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: PRKAR1B NM_001164760.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.02

Genes affected

PRKAR1B (HGNC:9390): (protein kinase cAMP-dependent type I regulatory subunit beta) The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRKAR1B	NM_001164760.2	c.917G>T	p.Arg306Leu	missense_variant	Exon 10 of 11	ENST00000537384.6	NP_001158232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRKAR1B	ENST00000537384.6	c.917G>T	p.Arg306Leu	missense_variant	Exon 10 of 11	5	NM_001164760.2	ENSP00000440449.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000213 AC: 3 AN: 1406502 Hom.: 0 Cov.: 31 AF XY: 0.00000288 AC XY: 2 AN XY: 694382

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000276

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: 0.00000185

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.56
BayesDel_addAF	Pathogenic	0.28	D
BayesDel_noAF	Pathogenic	0.16
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.79	D;D;D;D;D
Eigen	Benign	-0.099
Eigen_PC	Benign	0.048
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;.;.;.;.
M_CAP	Benign	0.075	D
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.72	N;N;N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Pathogenic	-5.0	D;D;D;D;D
REVEL	Uncertain	0.52
Sift	Benign	0.17	T;T;T;T;T
Sift4G	Benign	0.25	T;T;T;T;T
Polyphen		0.027	B;B;B;B;B
Vest4		0.82
MutPred		0.40		Loss of disorder (P = 0.0467);Loss of disorder (P = 0.0467);Loss of disorder (P = 0.0467);Loss of disorder (P = 0.0467);Loss of disorder (P = 0.0467);
MVP		0.87
MPC		0.92
ClinPred		0.95	D
GERP RS		4.5
Varity_R		0.71
gMVP		0.74

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: rs866622752; hg19: chr7-591082;