rs550769703

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.1539C>T(p.Pro513Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00598 in 1,525,452 control chromosomes in the GnomAD database, including 860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position has been classified as Pathogenic.

Frequency

Genomes: 𝑓 0.012 ( 109 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 751 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.46

Publications

0 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 Gene-Disease associations (from GenCC):

autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
polycystic kidney disease 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
autosomal recessive polycystic kidney disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Caroli disease
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp

PKD1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 16-2116900-G-A is Benign according to our data. Variant chr16-2116900-G-A is described in ClinVar as Benign. ClinVar VariationId is 256925.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.46 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.1539C>T	p.Pro513Pro	synonymous_variant	Exon 7 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.1539C>T	p.Pro513Pro	synonymous_variant	Exon 7 of 46	1	NM_001009944.3	ENSP00000262304.4

Frequencies

GnomAD3 genomes

AF:

0.0117

AC:

1781

AN:

152226

Hom.:

107

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00328

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000367

Gnomad OTH

AF:

0.0167

GnomAD2 exomes

AF:

0.0380

AC:

4948

AN:

130094

AF XY:

0.0278

show subpopulations

Gnomad AFR exome

AF:

0.00297

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000476

Gnomad FIN exome

AF:

0.000559

Gnomad NFE exome

AF:

0.000205

Gnomad OTH exome

AF:

0.0292

GnomAD4 exome

AF:

0.00534

AC:

7332

AN:

1373108

Hom.:

751

Cov.:

AF XY:

0.00455

AC XY:

3090

AN XY:

679226

show subpopulations

African (AFR)

AF:

0.00196

AC:

AN:

31572

American (AMR)

AF:

0.183

AC:

6676

AN:

36470

Ashkenazi Jewish (ASJ)

AF:

0.0000399

AC:

AN:

25064

East Asian (EAS)

AF:

0.00147

AC:

AN:

36138

South Asian (SAS)

AF:

0.000188

AC:

AN:

79750

European-Finnish (FIN)

AF:

0.00100

AC:

AN:

33972

Middle Eastern (MID)

AF:

0.000248

AC:

AN:

4040

European-Non Finnish (NFE)

AF:

0.000187

AC:

200

AN:

1068756

Other (OTH)

AF:

0.00506

AC:

290

AN:

57346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

457

913

1370

1826

2283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<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:

0.0117

AC:

1790

AN:

152344

Hom.:

109

Cov.:

AF XY:

0.0122

AC XY:

908

AN XY:

74494

show subpopulations

African (AFR)

AF:

0.00327

AC:

136

AN:

41590

American (AMR)

AF:

0.103

AC:

1582

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68022

Other (OTH)

AF:

0.0166

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

176

265

353

441

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00679

Hom.:

Bravo

AF:

0.0217

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 25, 2025

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jan 30, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Polycystic kidney disease, adult type

Benign:1

Feb 27, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Polycystic kidney disease

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The PKD1 p.Pro513= variant was identified in 1 of 460 proband chromosomes (frequency: 0.002) from individuals or families with ADPKD (Rossetti 2012). The variant was also identified in dbSNP (ID: rs550769703) as â€šÃ„ÃºWith Benign alleleâ€šÃ„Ã¹, ClinVar (classified as benign by Prevention Genetics), ADPKD Mutation Database (likely neutral). This variant was identified in the 1000 Genomes Project in 110 of 5000 chromosomes (frequency: 0.022), the Genome Aggregation Database (beta, October 19th 2016) in 5209 (593 homozygous) of 130176 chromosomes (freq. 0.04), the Exome Aggregation Consortium database (August 8th 2016) in 23 (1 homozygous) of 11406 chromosomes (freq. 0.002) in the following populations: Latino in 17 of 158 chromosomes (freq. 0.1), European in 5 of 3112 chromosomes (freq. 0.002), South Asian in 1 of 7474 chromosomes (freq. 0.0001), but was not seen in African, Finnish, East Asian and Other populations, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was not found in Clinvitae, GeneInsight COGR, MutDB, PKD1-LOVD or PKD1-LOVD 3.0 databases. The p.Pro513Pro variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory criteria to be classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.049

(source)

DANN

Benign

0.90

PhyloP100

-4.5

Mutation Taster

=99/1

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over