rs41280442
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The ENST00000373980.11(PRKG1):c.1174-15C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,610,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
PRKG1
ENST00000373980.11 splice_polypyrimidine_tract, intron
ENST00000373980.11 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.527
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=-0.84).
BP6
Variant 10-52271335-C-T is Benign according to our data. Variant chr10-52271335-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 516011.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
High AC in GnomAdExome4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1174-15C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000373980.11 | NP_006249.1 | |||
PRKG1 | NM_001098512.3 | c.1129-15C>T | splice_polypyrimidine_tract_variant, intron_variant | NP_001091982.1 | ||||
PRKG1 | NM_001374781.1 | c.-36-15C>T | splice_polypyrimidine_tract_variant, intron_variant | NP_001361710.1 | ||||
PRKG1 | XM_017016413.2 | c.871-15C>T | splice_polypyrimidine_tract_variant, intron_variant | XP_016871902.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1174-15C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_006258.4 | ENSP00000363092 | ||||
PRKG1-AS1 | ENST00000452247.7 | n.461+22580G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152102Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1457946Hom.: 0 Cov.: 30 AF XY: 0.00000965 AC XY: 7AN XY: 725450
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74402
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 06, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Aortic aneurysm, familial thoracic 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2023 | - - |
Connective tissue disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Jun 01, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at