rs377419559
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001009944.3(PKD1):c.11538-10C>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 0.0000115 in 1,561,070 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 0.000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000057 ( 0 hom. )
Consequence
PKD1
NM_001009944.3 splice_polypyrimidine_tract, intron
NM_001009944.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.00006439
2
Clinical Significance
Conservation
PhyloP100: -0.295
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 -10 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.81).
BP6
?
Variant 16-2091607-G-A is Benign according to our data. Variant chr16-2091607-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 256904.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
?
High AC in GnomAd at 10 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PKD1 | NM_001009944.3 | c.11538-10C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000262304.9 | |||
PKD1-AS1 | NR_135175.1 | n.172G>A | non_coding_transcript_exon_variant | 1/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PKD1 | ENST00000262304.9 | c.11538-10C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001009944.3 | P5 | |||
PKD1-AS1 | ENST00000563284.3 | n.69G>A | splice_region_variant, non_coding_transcript_exon_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152116Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.00000581 AC: 1AN: 172080Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 95814
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GnomAD4 exome AF: 0.00000568 AC: 8AN: 1408954Hom.: 0 Cov.: 32 AF XY: 0.00000717 AC XY: 5AN XY: 697572
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GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152116Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74310
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
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dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at