rs9935526

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.5172C>T(p.Ala1724Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.173 in 1,609,216 control chromosomes in the GnomAD database, including 29,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 6284 hom., cov: 33)

Exomes 𝑓: 0.17 ( 22756 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.914

Publications

17 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=-0.89).

BP6

Variant 16-2109995-G-A is Benign according to our data. Variant chr16-2109995-G-A is described in ClinVar as Benign. ClinVar VariationId is 256974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.914 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.5172C>T	p.Ala1724Ala	synonymous_variant	Exon 15 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.5172C>T	p.Ala1724Ala	synonymous_variant	Exon 15 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.246

AC:

37417

AN:

152074

Hom.:

6269

Cov.:

show subpopulations

Gnomad AFR

AF:

0.471

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.181

Gnomad ASJ

AF:

0.235

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0867

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.234

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.241

GnomAD2 exomes

AF:

0.161

AC:

38922

AN:

242448

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.486

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.232

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.166

Gnomad OTH exome

AF:

0.177

GnomAD4 exome

AF:

0.165

AC:

240747

AN:

1457024

Hom.:

22756

Cov.:

AF XY:

0.163

AC XY:

117821

AN XY:

724784

show subpopulations

African (AFR)

AF:

0.484

AC:

16149

AN:

33370

American (AMR)

AF:

0.119

AC:

5300

AN:

44606

Ashkenazi Jewish (ASJ)

AF:

0.238

AC:

6206

AN:

26102

East Asian (EAS)

AF:

0.000277

AC:

AN:

39672

South Asian (SAS)

AF:

0.0896

AC:

7713

AN:

86070

European-Finnish (FIN)

AF:

0.183

AC:

9484

AN:

51912

Middle Eastern (MID)

AF:

0.231

AC:

977

AN:

4226

European-Non Finnish (NFE)

AF:

0.166

AC:

184248

AN:

1110988

Other (OTH)

AF:

0.177

AC:

10659

AN:

60078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

12050

24100

36149

48199

60249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6622

13244

19866

26488

33110

<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:

0.246

AC:

37477

AN:

152192

Hom.:

6284

Cov.:

AF XY:

0.241

AC XY:

17950

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.471

AC:

19574

AN:

41520

American (AMR)

AF:

0.181

AC:

2762

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.235

AC:

817

AN:

3470

East Asian (EAS)

AF:

0.00135

AC:

AN:

5180

South Asian (SAS)

AF:

0.0863

AC:

417

AN:

4830

European-Finnish (FIN)

AF:

0.191

AC:

2025

AN:

10610

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11181

AN:

67974

Other (OTH)

AF:

0.238

AC:

503

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1323

2645

3968

5290

6613

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.196

Hom.:

1162

Bravo

AF:

0.257

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

Mar 27, 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

Sep 24, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22608885, 10364515) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Polycystic kidney disease, adult type

Benign:1

Jul 07, 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 c.5172C>T, p.Ala1724Ala variant was identified in 17% of 18662 control alleles in the Exome Aggregation Consortium (March 14, 2016). According to ACMG guidelines for variant classification based on allele frequency, category BA1, this variant is considered benign and has not been further reviewed (Richards 2015). -

Autosomal dominant polycystic kidney disease

Benign:1

Jan 01, 2019

Molecular Genetics of Inherited Kidney Disorders Laboratory, Garvan Institute of Medical Research

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.10

(source)

DANN

Benign

0.74

PhyloP100

-0.91

Mutation Taster

=100/0

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