16-2102128-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001009944.3(PKD1):c.9330T>C(p.Pro3110Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0677 in 1,536,054 control chromosomes in the GnomAD database, including 13,168 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 5904 hom., cov: 31)

Exomes 𝑓: 0.050 ( 7264 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -2.67

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.01).

BP6

Variant 16-2102128-A-G is Benign according to our data. Variant chr16-2102128-A-G is described in ClinVar as [Benign]. Clinvar id is 257042.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2102128-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-2.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.9330T>C	p.Pro3110Pro	synonymous_variant	Exon 26 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.9330T>C	p.Pro3110Pro	synonymous_variant	Exon 26 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.235

AC:

34200

AN:

145742

Hom.:

5893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.481

Gnomad AMI

AF:

0.0865

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.221

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0612

Gnomad FIN

AF:

0.168

Gnomad MID

AF:

0.232

Gnomad NFE

AF:

0.152

Gnomad OTH

AF:

0.226

GnomAD3 exomes

AF:

0.0326

AC:

7348

AN:

225576

Hom.:

1268

AF XY:

0.0291

AC XY:

3599

AN XY:

123668

show subpopulations

Gnomad AFR exome

AF:

0.250

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0374

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.0116

Gnomad FIN exome

AF:

0.00557

Gnomad NFE exome

AF:

0.0284

Gnomad OTH exome

AF:

0.0376

GnomAD4 exome

AF:

0.0501

AC:

69691

AN:

1390220

Hom.:

7264

Cov.:

AF XY:

0.0509

AC XY:

35249

AN XY:

692220

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.0637

Gnomad4 ASJ exome

AF:

0.130

Gnomad4 EAS exome

AF:

0.000202

Gnomad4 SAS exome

AF:

0.0402

Gnomad4 FIN exome

AF:

0.111

Gnomad4 NFE exome

AF:

0.0408

Gnomad4 OTH exome

AF:

0.0832

GnomAD4 genome

AF:

0.235

AC:

34242

AN:

145834

Hom.:

5904

Cov.:

AF XY:

0.227

AC XY:

16163

AN XY:

71092

show subpopulations

Gnomad4 AFR

AF:

0.481

Gnomad4 AMR

AF:

0.170

Gnomad4 ASJ

AF:

0.221

Gnomad4 EAS

AF:

0.00154

Gnomad4 SAS

AF:

0.0612

Gnomad4 FIN

AF:

0.168

Gnomad4 NFE

AF:

0.152

Gnomad4 OTH

AF:

0.224

Alfa

AF:

0.315

Hom.:

3897

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

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

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Polycystic kidney disease, adult type

Benign:2

Apr 11, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 07, 2020

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24374109, 11857740, 22608885, 22383692, 22008521, 18837007, 17574468, 10854095) -

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.Pro3110Pro variant was identified as a polymorphism in 92 of 658 proband chromosomes (frequency: 0.140) from individuals or families with ADPKD (McCluskey 2002, Garcia-Gonzalez 2007, Rossetti 2012). The variant was also identified in dbSNP (ID: rs144582212 â€šÃ„ÃºWith unknown alleleâ€šÃ„Ã¹, with a minor allele frequency of 0.1388 (695 of 5007 chromosomes in 1000 Genomes Project). The variant was not identified in the NHLBI Exome Sequencing Project (Exome Variant Server). This variant was identified in the Exome Aggregation Consortium (ExAC) database (March 14, 2016) in 20 of 69990 chromosomes (frequency: 0.0003) or 9 of 2566 African , 2 of 7098 Latino , 9 of 37172 European (Non-Finnish) chromosomes and was not found in populations of South Asians, East Asian, European (Finnish) and other. We cannot be certain that variant data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The variant was identified in Clinvitae by EmyClass and classified as benign. The variant was also identified in the PKD Mutation Database and classified as likely neutral. The p.Pro3110Pro 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. -

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

-1.0

CADD

Benign

0.063

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over