10-50991696-G-C

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001098512.3(PRKG1):​c.266+52G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00317 in 1,224,034 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0032 ( 15 hom. )

Consequence

PRKG1
NM_001098512.3 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.113
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.66).
BP6
Variant 10-50991696-G-C is Benign according to our data. Variant chr10-50991696-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1219572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAd4 at 419 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PRKG1NM_001098512.3 linkuse as main transcriptc.266+52G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PRKG1ENST00000401604.8 linkuse as main transcriptc.266+52G>C intron_variant 5 P1Q13976-1

Frequencies

GnomAD3 genomes
AF:
0.00278
AC:
419
AN:
150512
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000582
Gnomad AMI
AF:
0.00220
Gnomad AMR
AF:
0.000397
Gnomad ASJ
AF:
0.00116
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00124
Gnomad FIN
AF:
0.0127
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00367
Gnomad OTH
AF:
0.00193
GnomAD4 exome
AF:
0.00323
AC:
3467
AN:
1073414
Hom.:
15
AF XY:
0.00332
AC XY:
1704
AN XY:
512614
show subpopulations
Gnomad4 AFR exome
AF:
0.000582
Gnomad4 AMR exome
AF:
0.000611
Gnomad4 ASJ exome
AF:
0.000906
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00222
Gnomad4 FIN exome
AF:
0.0113
Gnomad4 NFE exome
AF:
0.00319
Gnomad4 OTH exome
AF:
0.00240
GnomAD4 genome
AF:
0.00278
AC:
419
AN:
150620
Hom.:
1
Cov.:
32
AF XY:
0.00318
AC XY:
234
AN XY:
73576
show subpopulations
Gnomad4 AFR
AF:
0.000581
Gnomad4 AMR
AF:
0.000397
Gnomad4 ASJ
AF:
0.00116
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00124
Gnomad4 FIN
AF:
0.0127
Gnomad4 NFE
AF:
0.00367
Gnomad4 OTH
AF:
0.00191
Alfa
AF:
0.00255
Hom.:
0
Bravo
AF:
0.00179

ClinVar

Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Likely benign, criteria provided, single submitterclinical testingGeneDxJul 26, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.66
CADD
Benign
4.5
DANN
Benign
0.89

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555654395; hg19: chr10-52751456; API