rs2369068
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001009944.3(PKD1):āc.3063T>Cā(p.Gly1021=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,606,556 control chromosomes in the GnomAD database, including 15,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ā ).
Frequency
Genomes: š 0.20 ( 5073 hom., cov: 33)
Exomes š: 0.10 ( 10630 hom. )
Consequence
PKD1
NM_001009944.3 synonymous
NM_001009944.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.34
Genes affected
PKD1 (HGNC:9008): (polycystin 1, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded glycoprotein contains a large N-terminal extracellular region, multiple transmembrane domains and a cytoplasmic C-tail. It is an integral membrane protein that functions as a regulator of calcium permeable cation channels and intracellular calcium homoeostasis. It is also involved in cell-cell/matrix interactions and may modulate G-protein-coupled signal-transduction pathways. It plays a role in renal tubular development, and mutations in this gene cause autosomal dominant polycystic kidney disease type 1 (ADPKD1). ADPKD1 is characterized by the growth of fluid-filled cysts that replace normal renal tissue and result in end-stage renal failure. Splice variants encoding different isoforms have been noted for this gene. Also, six pseudogenes, closely linked in a known duplicated region on chromosome 16p, have been described. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
Variant 16-2112886-A-G is Benign according to our data. Variant chr16-2112886-A-G is described in ClinVar as [Benign]. Clinvar id is 256942.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2112886-A-G is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=2.34 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.3063T>C | p.Gly1021= | synonymous_variant | 13/46 | ENST00000262304.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.3063T>C | p.Gly1021= | synonymous_variant | 13/46 | 1 | NM_001009944.3 | P5 | |
ENST00000568795.1 | n.161-161A>G | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.196 AC: 29808AN: 151862Hom.: 5057 Cov.: 33
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GnomAD3 exomes AF: 0.105 AC: 25957AN: 246982Hom.: 2781 AF XY: 0.0966 AC XY: 12964AN XY: 134200
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GnomAD4 exome AF: 0.102 AC: 147802AN: 1454576Hom.: 10630 Cov.: 35 AF XY: 0.0988 AC XY: 71494AN XY: 723778
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GnomAD4 genome ? AF: 0.197 AC: 29867AN: 151980Hom.: 5073 Cov.: 33 AF XY: 0.189 AC XY: 14023AN XY: 74292
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ClinVar
Significance: Benign
Submissions summary: Benign:6
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Polycystic kidney disease, adult type Benign:2
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jun 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Jul 07, 2020 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Polycystic kidney disease Benign:1
Benign, no assertion criteria provided | clinical testing | Department of Pathology and Laboratory Medicine, Sinai Health System | - | The c.3063T>C, p.Gly1021Gly variant was identified in 11% of 13209 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). - |
Autosomal dominant polycystic kidney disease Benign:1
Benign, criteria provided, single submitter | research | Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research | Jan 01, 2019 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 30, 2019 | This variant is associated with the following publications: (PMID: 10364515) - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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