10-50991310-A-AGCCGCCGCCGCC

Position:

• chr10-50991310-A-AGCCGCCGCCGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001098512.3(PRKG1):​c.-47_-36dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.045 (209 hom., cov: 0)
  • Exomes 𝑓: 0.043 (1210 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.42

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-50991310-A-AGCCGCCGCCGCC is Benign according to our data. Variant chr10-50991310-A-AGCCGCCGCCGCC is described in ClinVar as [Benign]. Clinvar id is 1296422.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.076 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-47_-36dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-47_-36dup		5_prime_UTR_variant	1/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6419 AN: 143722 Hom.: 209 Cov.: 0

Gnomad AFR AF: 0.0130

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.0832

Gnomad SAS AF: 0.0179

Gnomad FIN AF: 0.0805

Gnomad MID AF: 0.0131

Gnomad NFE AF: 0.0561

Gnomad OTH AF: 0.0485

GnomAD4 exome AF: 0.0426 AC: 52975 AN: 1243004 Hom.: 1210 Cov.: 13 AF XY: 0.0421 AC XY: 25784 AN XY: 612848

Gnomad4 AFR exome AF: 0.00684

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.0305

Gnomad4 EAS exome AF: 0.0858

Gnomad4 SAS exome AF: 0.00441

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0456

Gnomad4 OTH exome AF: 0.0360

GnomAD4 genome AF: 0.0446 AC: 6417 AN: 143820 Hom.: 209 Cov.: 0 AF XY: 0.0454 AC XY: 3168 AN XY: 69826

Gnomad4 AFR AF: 0.0129

Gnomad4 AMR AF: 0.0407

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.0830

Gnomad4 SAS AF: 0.0176

Gnomad4 FIN AF: 0.0805

Gnomad4 NFE AF: 0.0561

Gnomad4 OTH AF: 0.0479

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 19, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79957958; hg19: chr10-52751070;