rs45478794

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009944.3(PKD1):c.10529C>T(p.Thr3510Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0132 in 1,605,754 control chromosomes in the GnomAD database, including 645 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T3510T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 45 hom., cov: 33)

Exomes 𝑓: 0.013 ( 600 hom. )

Consequence

PKD1
NM_001009944.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.865

Publications

25 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022667646).

BP6

Variant 16-2094181-G-A is Benign according to our data. Variant chr16-2094181-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 256891.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0959 is higher than 0.05.

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	UniProt
PKD1	NM_001009944.3	MANE Select	c.10529C>T	p.Thr3510Met	missense	Exon 35 of 46	NP_001009944.3	P98161-1
PKD1	NM_000296.4		c.10526C>T	p.Thr3509Met	missense	Exon 35 of 46	NP_000287.4
PKD1-AS1	NR_135175.1		n.304-540G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PKD1	ENST00000262304.9	TSL:1 MANE Select	c.10529C>T	p.Thr3510Met	missense	Exon 35 of 46	ENSP00000262304.4	P98161-1
PKD1	ENST00000423118.5	TSL:1	c.10526C>T	p.Thr3509Met	missense	Exon 35 of 46	ENSP00000399501.1	P98161-3
PKD1	ENST00000487932.5	TSL:5	n.*1722C>T		non_coding_transcript_exon	Exon 22 of 30	ENSP00000457132.1	H3BTE0

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1621

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00200

Gnomad AMI

AF:

0.0241

Gnomad AMR

AF:

0.00255

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.0575

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.00621

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00855

Gnomad OTH

AF:

0.00766

GnomAD2 exomes

AF:

0.0209

AC:

4944

AN:

236058

AF XY:

0.0248

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.00319

Gnomad ASJ exome

AF:

0.00177

Gnomad EAS exome

AF:

0.0579

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.00730

Gnomad OTH exome

AF:

0.0136

GnomAD4 exome

AF:

0.0135

AC:

19585

AN:

1453432

Hom.:

600

Cov.:

AF XY:

0.0160

AC XY:

11534

AN XY:

722754

show subpopulations

African (AFR)

AF:

0.00204

AC:

AN:

33386

American (AMR)

AF:

0.00314

AC:

139

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.00185

AC:

AN:

25970

East Asian (EAS)

AF:

0.0521

AC:

2065

AN:

39598

South Asian (SAS)

AF:

0.0944

AC:

8038

AN:

85176

European-Finnish (FIN)

AF:

0.00669

AC:

346

AN:

51694

Middle Eastern (MID)

AF:

0.0116

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00715

AC:

7921

AN:

1107436

Other (OTH)

AF:

0.0149

AC:

893

AN:

60108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

1051

2101

3152

4202

5253

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

354

708

1062

1416

1770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0106

AC:

1614

AN:

152322

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

938

AN XY:

74486

show subpopulations

African (AFR)

AF:

0.00200

AC:

AN:

41564

American (AMR)

AF:

0.00255

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3472

East Asian (EAS)

AF:

0.0575

AC:

298

AN:

5186

South Asian (SAS)

AF:

0.103

AC:

499

AN:

4828

European-Finnish (FIN)

AF:

0.00621

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00856

AC:

582

AN:

68026

Other (OTH)

AF:

0.00758

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

143

215

286

358

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0101

Hom.:

Bravo

AF:

0.00803

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00652

AC:

ExAC

AF:

0.0211

AC:

2547

Asia WGS

AF:

0.0500

AC:

175

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Polycystic kidney disease, adult type (2)

Autosomal dominant polycystic kidney disease (1)

Polycystic kidney disease (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.68

CADD

Benign

6.8

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.23

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.67

PhyloP100

0.86

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.1

REVEL

Benign

0.10

Sift

Benign

0.047

Sift4G

Benign

0.080

Polyphen

0.86

Vest4

0.039

ClinPred

0.0025

GERP RS

0.47

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.018

gMVP

0.32

Mutation Taster

=96/4

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over