16-2088881-G-GCGCGCGCACACACACACACACACACA
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting
The NM_001009944.3(PKD1):c.*845_*846insTGTGTGTGTGTGTGTGTGTGCGCGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000089 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0000036 ( 0 hom. )
Consequence
PKD1
NM_001009944.3 3_prime_UTR
NM_001009944.3 3_prime_UTR
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.365
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]
TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BS2
High AC in GnomAd4 at 13 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.*845_*846insTGTGTGTGTGTGTGTGTGTGCGCGCG | 3_prime_UTR_variant | Exon 46 of 46 | ENST00000262304.9 | NP_001009944.3 | ||
TSC2 | NM_000548.5 | c.*272_*273insGCGCGCACACACACACACACACACAC | 3_prime_UTR_variant | Exon 42 of 42 | ENST00000219476.9 | NP_000539.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304 | c.*845_*846insTGTGTGTGTGTGTGTGTGTGCGCGCG | 3_prime_UTR_variant | Exon 46 of 46 | 1 | NM_001009944.3 | ENSP00000262304.4 | |||
TSC2 | ENST00000219476.9 | c.*272_*273insGCGCGCACACACACACACACACACAC | 3_prime_UTR_variant | Exon 42 of 42 | 5 | NM_000548.5 | ENSP00000219476.3 |
Frequencies
GnomAD3 genomes AF: 0.0000887 AC: 13AN: 146610Hom.: 0 Cov.: 0
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GnomAD4 exome AF: 0.00000364 AC: 1AN: 274764Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 145206
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GnomAD4 genome AF: 0.0000886 AC: 13AN: 146714Hom.: 0 Cov.: 0 AF XY: 0.0000697 AC XY: 5AN XY: 71758
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ClinVar
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at