16-2090009-A-G

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.12630T>C(p.Pro4210Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,608,974 control chromosomes in the GnomAD database, including 41,941 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 10754 hom., cov: 34)

Exomes 𝑓: 0.19 ( 31187 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -7.93

Publications

21 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:

MIR1225 (HGNC:33931): (microRNA 1225) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR1225 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=-1.01).

BP6

Variant 16-2090009-A-G is Benign according to our data. Variant chr16-2090009-A-G is described in ClinVar as Benign. ClinVar VariationId is 256921.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-7.93 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.12630T>C	p.Pro4210Pro	synonymous_variant	Exon 46 of 46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
PKD1	ENST00000262304.9 link	c.12630T>C	p.Pro4210Pro	synonymous_variant	Exon 46 of 46	1	NM_001009944.3	ENSP00000262304.4
PKD1	ENST00000423118.5 link	c.12627T>C	p.Pro4209Pro	synonymous_variant	Exon 46 of 46	1		ENSP00000399501.1
PKD1	ENST00000472577.1 link	n.658T>C		non_coding_transcript_exon_variant	Exon 3 of 3	2
MIR1225	ENST00000408729.1 link	n.*186T>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.309

AC:

46954

AN:

152060

Hom.:

10724

Cov.:

show subpopulations

Gnomad AFR

AF:

0.643

Gnomad AMI

AF:

0.0987

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.250

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0935

Gnomad FIN

AF:

0.233

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.185

Gnomad OTH

AF:

0.271

GnomAD2 exomes

AF:

0.188

AC:

44766

AN:

237720

AF XY:

0.180

show subpopulations

Gnomad AFR exome

AF:

0.648

Gnomad AMR exome

AF:

0.127

Gnomad ASJ exome

AF:

0.251

Gnomad EAS exome

AF:

0.000282

Gnomad FIN exome

AF:

0.224

Gnomad NFE exome

AF:

0.188

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.189

AC:

275325

AN:

1456796

Hom.:

31187

Cov.:

AF XY:

0.185

AC XY:

133823

AN XY:

724520

show subpopulations

African (AFR)

AF:

0.652

AC:

21811

AN:

33446

American (AMR)

AF:

0.136

AC:

5996

AN:

43984

Ashkenazi Jewish (ASJ)

AF:

0.257

AC:

6648

AN:

25910

East Asian (EAS)

AF:

0.000328

AC:

AN:

39594

South Asian (SAS)

AF:

0.0958

AC:

8228

AN:

85928

European-Finnish (FIN)

AF:

0.223

AC:

11531

AN:

51612

Middle Eastern (MID)

AF:

0.263

AC:

1513

AN:

5760

European-Non Finnish (NFE)

AF:

0.187

AC:

207116

AN:

1110418

Other (OTH)

AF:

0.207

AC:

12469

AN:

60144

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

13892

27784

41676

55568

69460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7350

14700

22050

29400

36750

<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:

0.309

AC:

47039

AN:

152178

Hom.:

10754

Cov.:

AF XY:

0.304

AC XY:

22625

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.643

AC:

26678

AN:

41498

American (AMR)

AF:

0.210

AC:

3217

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

867

AN:

3472

East Asian (EAS)

AF:

0.00155

AC:

AN:

5176

South Asian (SAS)

AF:

0.0932

AC:

450

AN:

4828

European-Finnish (FIN)

AF:

0.233

AC:

2470

AN:

10604

Middle Eastern (MID)

AF:

0.272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.186

AC:

12612

AN:

67986

Other (OTH)

AF:

0.268

AC:

567

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1406

2812

4219

5625

7031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<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:

0.190

Hom.:

1222

Bravo

AF:

0.322

Asia WGS

AF:

0.0860

AC:

300

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

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

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Polycystic kidney disease, adult type

Benign:2

May 23, 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

Sep 24, 2019

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

Benign:1

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

The 12630T>C, p.Pro4210Pro variant was identified in 20.11% of 21171 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

-1.0

CADD

Benign

0.13

(source)

DANN

Benign

0.39

PhyloP100

-7.9

Mutation Taster

=88/12

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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