chr10-52264069-T-C

Variant names:

• chr10-52264069-T-C
• rs16913596
• NM_006258.4:c.1174-7281T>C

Variant summary

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

The NM_006258.4(PRKG1):​c.1174-7281T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,200 control chromosomes in the GnomAD database, including 493 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 0.039 (493 hom., cov: 33)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.33 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.1174-7281T>C		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.1129-7281T>C		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374781.1		c.-36-7281T>C		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.1174-7281T>C		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1-AS1	ENST00000426785.2	TSL:1	n.170-10629A>G		intron	N/A
	PRKG1	ENST00000401604.8	TSL:5	c.1129-7281T>C		intron	N/A	ENSP00000384200.4	Q13976-1

Frequencies

GnomAD3 genomes AF: 0.0387 AC: 5881 AN: 152080 Hom.: 493 Cov.: 33

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0479

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00882

Gnomad OTH AF: 0.0330

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

GnomAD4 genome AF: 0.0387 AC: 5891 AN: 152200 Hom.: 493 Cov.: 33 AF XY: 0.0442 AC XY: 3289 AN XY: 74402

African (AFR) AF: 0.0169 AC: 701 AN: 41562

American (AMR) AF: 0.113 AC: 1722 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1769 AN: 5154

South Asian (SAS) AF: 0.103 AC: 499 AN: 4824

European-Finnish (FIN) AF: 0.0479 AC: 509 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00882 AC: 600 AN: 67990

Other (OTH) AF: 0.0313 AC: 66 AN: 2112

Alfa AF: 0.0202 Hom.: 541

Bravo AF: 0.0442

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.37
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16913596; hg19: chr10-54023829;