rs1177160264
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2
The NM_006258.4(PRKG1):āc.1845A>Gā(p.Ser615=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,607,102 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 (ā ā ).
Frequency
Genomes: š 0.000020 ( 0 hom., cov: 32)
Exomes š: 0.0000055 ( 0 hom. )
Consequence
PRKG1
NM_006258.4 synonymous
NM_006258.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.75
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 -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.39).
BP6
?
Variant 10-52288943-A-G is Benign according to our data. Variant chr10-52288943-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 477774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=1.75 with no splicing effect.
BS2
?
High AC in GnomAdExome4 at 8 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PRKG1 | NM_006258.4 | c.1845A>G | p.Ser615= | synonymous_variant | 16/18 | ENST00000373980.11 | |
PRKG1 | NM_001098512.3 | c.1800A>G | p.Ser600= | synonymous_variant | 16/18 | ||
PRKG1 | NM_001374781.1 | c.636A>G | p.Ser212= | synonymous_variant | 12/14 | ||
PRKG1 | XM_017016413.2 | c.1542A>G | p.Ser514= | synonymous_variant | 16/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PRKG1 | ENST00000373980.11 | c.1845A>G | p.Ser615= | synonymous_variant | 16/18 | 1 | NM_006258.4 | ||
PRKG1-AS1 | ENST00000452247.7 | n.461+4972T>C | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000550 AC: 8AN: 1454916Hom.: 0 Cov.: 31 AF XY: 0.00000553 AC XY: 4AN XY: 723758
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74336
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 11, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Aortic aneurysm, familial thoracic 8 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 04, 2022 | - - |
Computational scores
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Name
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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