10-52209518-G-A

Variant names:

• chr10-52209518-G-A
• rs10508965
• NM_006258.4:c.1077-42052G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006258.4(PRKG1):​c.1077-42052G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0862 in 152,120 control chromosomes in the GnomAD database, including 1,109 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.086 (1109 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 2 publications found

Genes affected

PRKG1 (HGNC:9414): (protein kinase cGMP-dependent 1) Mammals have three different isoforms of cyclic GMP-dependent protein kinase (Ialpha, Ibeta, and II). These PRKG isoforms act as key mediators of the nitric oxide/cGMP signaling pathway and are important components of many signal transduction processes in diverse cell types. This PRKG1 gene on human chromosome 10 encodes the soluble Ialpha and Ibeta isoforms of PRKG by alternative transcript splicing. A separate gene on human chromosome 4, PRKG2, encodes the membrane-bound PRKG isoform II. The PRKG1 proteins play a central role in regulating cardiovascular and neuronal functions in addition to relaxing smooth muscle tone, preventing platelet aggregation, and modulating cell growth. This gene is most strongly expressed in all types of smooth muscle, platelets, cerebellar Purkinje cells, hippocampal neurons, and the lateral amygdala. Isoforms Ialpha and Ibeta have identical cGMP-binding and catalytic domains but differ in their leucine/isoleucine zipper and autoinhibitory sequences and therefore differ in their dimerization substrates and kinase enzyme activity. [provided by RefSeq, Sep 2011]

PRKG1-AS1 (HGNC:45029): (PRKG1 antisense RNA 1)

LOC124902425 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006258.4. 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
	PRKG1	NM_006258.4	MANE Select	c.1077-42052G>A		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.1032-42052G>A		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374781.1		c.-133-42052G>A		intron	N/A	NP_001361710.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRKG1	ENST00000373980.11	TSL:1 MANE Select	c.1077-42052G>A		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1	ENST00000401604.8	TSL:5	c.1032-42052G>A		intron	N/A	ENSP00000384200.4	Q13976-1
	PRKG1	ENST00000672084.1		c.228-42052G>A		intron	N/A	ENSP00000499822.1	A0A5F9ZGW0

Frequencies

GnomAD3 genomes AF: 0.0862 AC: 13096 AN: 152002 Hom.: 1108 Cov.: 32

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0718

Gnomad ASJ AF: 0.0721

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0338

Gnomad FIN AF: 0.00915

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0319

Gnomad OTH AF: 0.0852

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0862 AC: 13114 AN: 152120 Hom.: 1109 Cov.: 32 AF XY: 0.0838 AC XY: 6231 AN XY: 74356

African (AFR) AF: 0.220 AC: 9123 AN: 41452

American (AMR) AF: 0.0716 AC: 1094 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0721 AC: 250 AN: 3466

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5174

South Asian (SAS) AF: 0.0336 AC: 162 AN: 4822

European-Finnish (FIN) AF: 0.00915 AC: 97 AN: 10596

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0319 AC: 2173 AN: 68018

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0187 Hom.: 24

Bravo AF: 0.0964

Asia WGS AF: 0.0270 AC: 97 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.5
DANN	Benign	0.48
PhyloP100		-0.041
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10508965; hg19: chr10-53969278;