16-2110502-T-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.4665A>C(p.Ala1555Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,612,016 control chromosomes in the GnomAD database, including 30,363 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 (i.e. A1555A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.25 ( 6671 hom., cov: 34)

Exomes 𝑓: 0.17 ( 23692 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.74

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=-0.57).

BP6

Variant 16-2110502-T-G is Benign according to our data. Variant chr16-2110502-T-G is described in ClinVar as [Benign]. Clinvar id is 256968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2110502-T-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.74 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.483 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.4665A>C	p.Ala1555Ala	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.4665A>C	p.Ala1555Ala	synonymous_variant	Exon 15 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38340

AN:

152084

Hom.:

6649

Cov.:

show subpopulations

Gnomad AFR

AF:

0.488

Gnomad AMI

AF:

0.134

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.236

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0882

Gnomad FIN

AF:

0.191

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.246

GnomAD3 exomes

AF:

0.164

AC:

40642

AN:

248566

Hom.:

4767

AF XY:

0.158

AC XY:

21294

AN XY:

135148

show subpopulations

Gnomad AFR exome

AF:

0.502

Gnomad AMR exome

AF:

0.112

Gnomad ASJ exome

AF:

0.233

Gnomad EAS exome

AF:

0.000164

Gnomad SAS exome

AF:

0.0877

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.168

AC:

244989

AN:

1459814

Hom.:

23692

Cov.:

AF XY:

0.165

AC XY:

119809

AN XY:

726224

show subpopulations

Gnomad4 AFR exome

AF:

0.503

Gnomad4 AMR exome

AF:

0.121

Gnomad4 ASJ exome

AF:

0.239

Gnomad4 EAS exome

AF:

0.000277

Gnomad4 SAS exome

AF:

0.0900

Gnomad4 FIN exome

AF:

0.183

Gnomad4 NFE exome

AF:

0.168

Gnomad4 OTH exome

AF:

0.180

GnomAD4 genome

AF:

0.252

AC:

38409

AN:

152202

Hom.:

6671

Cov.:

AF XY:

0.248

AC XY:

18421

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.489

Gnomad4 AMR

AF:

0.185

Gnomad4 ASJ

AF:

0.236

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0878

Gnomad4 FIN

AF:

0.191

Gnomad4 NFE

AF:

0.166

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.154

Hom.:

696

Bravo

AF:

0.264

Asia WGS

AF:

0.0770

AC:

269

AN:

3478

EpiCase

AF:

0.179

EpiControl

AF:

0.177

ClinVar

Significance: Benign

Submissions summary: Benign:7

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

- -

not provided

Benign:2

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: 22008521) -

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.4665A>C, p.Ala1555Ala variant was identified in 16.87% of 20079 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

-0.57

CADD

Benign

3.8

DANN

Benign

0.67

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

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