dbSNP rs142455071: PKD1:p.Gly3784Val (chr16-2092107-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001009944.3(PKD1):c.11351G>T(p.Gly3784Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 33)

Consequence

PKD1
NM_001009944.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.24

Publications

1 publications found

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]

PKD1 links:

PKD1-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

PKD1-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PKD1	NM_001009944.3	MANE Select	c.11351G>T	p.Gly3784Val	missense	Exon 40 of 46	NP_001009944.3
PKD1	NM_000296.4		c.11348G>T	p.Gly3783Val	missense	Exon 40 of 46	NP_000287.4
PKD1-AS1	NR_135175.1		n.179+493C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.11351G>T	p.Gly3784Val	missense	Exon 40 of 46	ENSP00000262304.4
PKD1	ENST00000423118.5	TSL:1	c.11348G>T	p.Gly3783Val	missense	Exon 40 of 46	ENSP00000399501.1
PKD1	ENST00000485120.1	TSL:3	n.200G>T		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Polycystic kidney disease, adult type (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Benign

-0.079

Eigen_PC

Benign

-0.055

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.77

M_CAP

Pathogenic

0.40

MetaRNN

Uncertain

0.71

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.6

PhyloP100

1.2

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-4.2

REVEL

Uncertain

0.42

Sift

Benign

0.41

Sift4G

Benign

0.14

Polyphen

0.51

Vest4

0.60

MutPred

0.61

Loss of disorder (P = 0.0312)

MVP

0.94

ClinPred

0.66

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.84

gMVP

0.83

Mutation Taster

=45/55

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over