rs75510884

Positions:

chr16-2111795-G-A

Variant summary

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

The NM_001009944.3(PKD1):c.3372C>T(p.Ala1124=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0994 in 1,608,608 control chromosomes in the GnomAD database, including 9,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.14 ( 1985 hom., cov: 33)

Exomes 𝑓: 0.095 ( 7751 hom. )

Consequence

PKD1
NM_001009944.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.171

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=-0.89).

BP6

Variant 16-2111795-G-A is Benign according to our data. Variant chr16-2111795-G-A is described in ClinVar as [Benign]. Clinvar id is 256949.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-2111795-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.171 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.26 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1	NM_001009944.3 linkuse as main transcript	c.3372C>T	p.Ala1124=	synonymous_variant	15/46	ENST00000262304.9	NP_001009944.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 linkuse as main transcript	c.3372C>T	p.Ala1124=	synonymous_variant	15/46	1	NM_001009944.3	ENSP00000262304	P5	P98161-1

Frequencies

GnomAD3 genomes

AF:

0.139

AC:

21201

AN:

152046

Hom.:

1982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.123

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0279

Gnomad FIN

AF:

0.0759

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.0978

Gnomad OTH

AF:

0.147

GnomAD3 exomes

AF:

0.0888

AC:

21441

AN:

241434

Hom.:

1350

AF XY:

0.0847

AC XY:

11165

AN XY:

131754

show subpopulations

Gnomad AFR exome

AF:

0.272

Gnomad AMR exome

AF:

0.0701

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.0290

Gnomad FIN exome

AF:

0.0730

Gnomad NFE exome

AF:

0.0975

Gnomad OTH exome

AF:

0.107

GnomAD4 exome

AF:

0.0952

AC:

138674

AN:

1456444

Hom.:

7751

Cov.:

AF XY:

0.0933

AC XY:

67559

AN XY:

724404

show subpopulations

Gnomad4 AFR exome

AF:

0.274

Gnomad4 AMR exome

AF:

0.0773

Gnomad4 ASJ exome

AF:

0.143

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0317

Gnomad4 FIN exome

AF:

0.0703

Gnomad4 NFE exome

AF:

0.0982

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.140

AC:

21234

AN:

152164

Hom.:

1985

Cov.:

AF XY:

0.134

AC XY:

9968

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.264

Gnomad4 AMR

AF:

0.111

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0275

Gnomad4 FIN

AF:

0.0759

Gnomad4 NFE

AF:

0.0979

Gnomad4 OTH

AF:

0.145

Alfa

AF:

0.117

Hom.:

443

Bravo

AF:

0.151

Asia WGS

AF:

0.0300

AC:

107

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 01, 2017	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 25, 2019	This variant is associated with the following publications: (PMID: 11967008) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Polycystic kidney disease, adult type

Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Jul 07, 2020

- -

Polycystic kidney disease

Benign:1

Benign, no assertion criteria provided

clinical testing

Department of Pathology and Laboratory Medicine, Sinai Health System

The c.3372C>T, p.Ala1124Ala variant was identified in10.66% of 10299 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

Benign, criteria provided, single submitter

research

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

Jan 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.12

DANN

Benign

0.75

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