16-2112393-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001009944.3(PKD1):​c.3242C>G​(p.Ser1081Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,434,730 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 7.0e-7 ( 0 hom. )

Consequence

PKD1
NM_001009944.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.05
Variant links:
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 Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.38229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKD1NM_001009944.3 linkc.3242C>G p.Ser1081Trp missense_variant Exon 14 of 46 ENST00000262304.9 NP_001009944.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PKD1ENST00000262304.9 linkc.3242C>G p.Ser1081Trp missense_variant Exon 14 of 46 1 NM_001009944.3 ENSP00000262304.4 P98161-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.97e-7
AC:
1
AN:
1434730
Hom.:
0
Cov.:
32
AF XY:
0.00000140
AC XY:
1
AN XY:
713868
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.10
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.38
T;.
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.28
FATHMM_MKL
Benign
0.096
N
LIST_S2
Benign
0.84
T;T
M_CAP
Uncertain
0.27
D
MetaRNN
Benign
0.38
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.3
L;L
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-2.6
D;D
REVEL
Benign
0.082
Sift
Uncertain
0.0050
D;D
Sift4G
Uncertain
0.0050
D;D
Polyphen
1.0
D;D
Vest4
0.32
MutPred
0.52
Gain of catalytic residue at S1081 (P = 5e-04);Gain of catalytic residue at S1081 (P = 5e-04);
MVP
0.71
ClinPred
0.74
D
GERP RS
1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.10
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2162394; API