rs724159972

Variant names:

• chr9-69013871-G-C
• rs724159972
• NM_002732.4:c.222C>G
• PRKACG p.Ile74Met

Your query was ambiguous. Multiple possible variants found:

• chr9-69013871-G-C
• chr9-69013871-G-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_002732.4(PRKACG):​c.222C>G​(p.Ile74Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as no classifications from unflagged records (no stars).

• Frequency: Genomes: not found (cov: 30)
• Consequence: PRKACG NM_002732.4 missense
• Clinical Significance: no classifications from unflagged records no classifications from unflagged records P:1
• Conservation: PhyloP100: 0.0890
• Publications: 5 publications found

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]

PRKACG Gene-Disease associations (from GenCC):

• platelet-type bleeding disorder 19

  Inheritance: AR Classification: SUPPORTIVE, LIMITED, NO_KNOWN Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACG	NM_002732.4	MANE Select	c.222C>G	p.Ile74Met	missense	Exon 1 of 1	NP_002723.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKACG	ENST00000377276.5	TSL:6 MANE Select	c.222C>G	p.Ile74Met	missense	Exon 1 of 1	ENSP00000366488.2	P22612

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 30

ClinVar

ClinVar submissions

Significance: no classifications from unflagged records

Revision: no classifications from unflagged records

Pathogenic	VUS	Benign	Condition
1	-	-	Platelet-type bleeding disorder 19 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.047	N
LIST_S2	Uncertain	0.95	D
M_CAP	Pathogenic	0.43	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.089
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-2.2	N
REVEL	Pathogenic	0.69
Sift	Benign	0.030	D
Sift4G	Benign	0.16	T
PromoterAI		-0.060	Neutral
Varity_R		0.22
gMVP		0.28
Mutation Taster		=84/16	disease causing (ClinVar)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs724159972;

hg19: chr9-71628787;