10-50991310-A-AGCCGCC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001098512.3(PRKG1):c.-41_-36dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (25 hom., cov: 0)
  • Exomes 𝑓: 0.012 (146 hom.)
• Consequence: PRKG1 NM_001098512.3 5_prime_UTR
• Clinical Significance: Likely 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-AGCCGCC is Benign according to our data. Variant chr10-50991310-A-AGCCGCC is described in ClinVar as [Likely_benign]. Clinvar id is 1178642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0128 (1841/143912) while in subpopulation SAS AF= 0.0234 (106/4536). AF 95% confidence interval is 0.0198. There are 25 homozygotes in gnomad4. There are 963 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd at 1840 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRKG1	NM_001098512.3	c.-41_-36dup		5_prime_UTR_variant	1/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRKG1	ENST00000401604.8	c.-41_-36dup		5_prime_UTR_variant	1/18	5		P1

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1840 AN: 143814 Hom.: 25 Cov.: 0

Gnomad AFR AF: 0.0113

Gnomad AMI AF: 0.00115

Gnomad AMR AF: 0.00919

Gnomad ASJ AF: 0.00891

Gnomad EAS AF: 0.00182

Gnomad SAS AF: 0.0238

Gnomad FIN AF: 0.0233

Gnomad MID AF: 0.0196

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0148

GnomAD4 exome AF: 0.0125 AC: 15604 AN: 1251372 Hom.: 146 Cov.: 13 AF XY: 0.0127 AC XY: 7824 AN XY: 616584

Gnomad4 AFR exome AF: 0.00973

Gnomad4 AMR exome AF: 0.00323

Gnomad4 ASJ exome AF: 0.00819

Gnomad4 EAS exome AF: 0.00325

Gnomad4 SAS exome AF: 0.0173

Gnomad4 FIN exome AF: 0.0141

Gnomad4 NFE exome AF: 0.0127

Gnomad4 OTH exome AF: 0.0120

GnomAD4 genome AF: 0.0128 AC: 1841 AN: 143912 Hom.: 25 Cov.: 0 AF XY: 0.0138 AC XY: 963 AN XY: 69878

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.00917

Gnomad4 ASJ AF: 0.00891

Gnomad4 EAS AF: 0.00205

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0233

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0146

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 13, 2019

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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;