rs1555453244
Variant names:
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Likely pathogenic. The variant received 8 ACMG points: 8P and 0B. PM2PM5PP3_Strong
The NM_001009944.3(PKD1):c.7214G>T(p.Trp2405Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W2405G) has been classified as Likely pathogenic.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
PKD1
NM_001009944.3 missense
NM_001009944.3 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 7.44
Publications
2 publications found
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]
MIR6511B1 (HGNC:50228): (microRNA 6511b-1) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_pathogenic. The variant received 8 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM5
Other missense variant is known to change same aminoacid residue: Variant chr16-2106674-A-C is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 2634378.Status of the report is criteria_provided_single_submitter, 1 stars.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| PKD1 | TSL:1 MANE Select | c.7214G>T | p.Trp2405Leu | missense | Exon 18 of 46 | ENSP00000262304.4 | P98161-1 | ||
| PKD1 | TSL:1 | c.7214G>T | p.Trp2405Leu | missense | Exon 18 of 46 | ENSP00000399501.1 | P98161-3 | ||
| PKD1 | TSL:5 | c.380G>T | p.Trp127Leu | missense | Exon 5 of 5 | ENSP00000456670.1 | H3BSE8 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1441036Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 717492
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
AC:
0
AN:
1441036
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
717492
African (AFR)
AF:
AC:
0
AN:
33310
American (AMR)
AF:
AC:
0
AN:
44500
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26038
East Asian (EAS)
AF:
AC:
0
AN:
39630
South Asian (SAS)
AF:
AC:
0
AN:
85812
European-Finnish (FIN)
AF:
AC:
0
AN:
39132
Middle Eastern (MID)
AF:
AC:
0
AN:
4128
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1108584
Other (OTH)
AF:
AC:
0
AN:
59902
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Pathogenic
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Gain of disorder (P = 0.0172)
MVP
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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