chr9-69012840-G-C

Position:

• chr9-69012840-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002732.4(PRKACG):​c.*197C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0795 in 572,552 control chromosomes in the GnomAD database, including 2,707 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.083 (619 hom., cov: 30)
  • Exomes 𝑓: 0.078 (2088 hom.)
• Consequence: PRKACG NM_002732.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0300

Genes affected

PRKACG (HGNC:9382): (protein kinase cAMP-activated catalytic subunit gamma) Cyclic AMP-dependent protein kinase (PKA) consists of two catalytic subunits and a regulatory subunit dimer. This gene encodes the gamma form of its catalytic subunit. The gene is intronless and is thought to be a retrotransposon derived from the gene for the alpha form of the PKA catalytic subunit. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 9-69012840-G-C is Benign according to our data. Variant chr9-69012840-G-C is described in ClinVar as [Benign]. Clinvar id is 1251250.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRKACG	NM_002732.4	c.*197C>G		3_prime_UTR_variant	1/1	ENST00000377276.5	NP_002723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRKACG	ENST00000377276.5	c.*197C>G		3_prime_UTR_variant	1/1		NM_002732.4	ENSP00000366488	P1

Frequencies

GnomAD3 genomes AF: 0.0832 AC: 12096 AN: 145382 Hom.: 620 Cov.: 30

Gnomad AFR AF: 0.0985

Gnomad AMI AF: 0.0927

Gnomad AMR AF: 0.134

Gnomad ASJ AF: 0.0965

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.0878

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0782 AC: 33402 AN: 427062 Hom.: 2088 Cov.: 4 AF XY: 0.0776 AC XY: 17382 AN XY: 224038

Gnomad4 AFR exome AF: 0.0934

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.0870

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.0899

Gnomad4 FIN exome AF: 0.0486

Gnomad4 NFE exome AF: 0.0515

Gnomad4 OTH exome AF: 0.0791

GnomAD4 genome AF: 0.0832 AC: 12105 AN: 145490 Hom.: 619 Cov.: 30 AF XY: 0.0840 AC XY: 5966 AN XY: 71010

Gnomad4 AFR AF: 0.0985

Gnomad4 AMR AF: 0.135

Gnomad4 ASJ AF: 0.0965

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.0498

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0767

Alfa AF: 0.0212 Hom.: 9

Bravo AF: 0.0892

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 21, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.61

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: rs3812538; hg19: chr9-71627756;