10-52170031-T-C

Variant names:

• chr10-52170031-T-C
• rs11001056
• NM_006258.4:c.1076+8068T>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.1076+8068T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 152,102 control chromosomes in the GnomAD database, including 18,096 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 0.44 (18096 hom., cov: 32)
• Consequence: PRKG1 NM_006258.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 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.1076+8068T>C		intron	N/A	NP_006249.1	Q13976-2
	PRKG1	NM_001098512.3		c.1031+8068T>C		intron	N/A	NP_001091982.1	Q13976-1
	PRKG1	NM_001374781.1		c.-134+8068T>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.1076+8068T>C		intron	N/A	ENSP00000363092.5	Q13976-2
	PRKG1	ENST00000401604.8	TSL:5	c.1031+8068T>C		intron	N/A	ENSP00000384200.4	Q13976-1
	PRKG1	ENST00000672084.1		c.227+8068T>C		intron	N/A	ENSP00000499822.1	A0A5F9ZGW0

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67517 AN: 151984 Hom.: 18085 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.460

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.535

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.463

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

GnomAD4 genome AF: 0.444 AC: 67538 AN: 152102 Hom.: 18096 Cov.: 32 AF XY: 0.440 AC XY: 32699 AN XY: 74338

African (AFR) AF: 0.154 AC: 6407 AN: 41526

American (AMR) AF: 0.608 AC: 9292 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.460 AC: 1595 AN: 3470

East Asian (EAS) AF: 0.208 AC: 1074 AN: 5166

South Asian (SAS) AF: 0.384 AC: 1844 AN: 4808

European-Finnish (FIN) AF: 0.535 AC: 5651 AN: 10564

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40079 AN: 67970

Other (OTH) AF: 0.463 AC: 976 AN: 2108

Alfa AF: 0.531 Hom.: 74543

Bravo AF: 0.438

Asia WGS AF: 0.279 AC: 970 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.2
DANN	Benign	0.42
PhyloP100		0.12
Mutation Taster		=100/0	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: rs11001056; hg19: chr10-53929791;