NM_001009944.3:c.*861G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001009944.3(PKD1):c.*861G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00774 in 505,202 control chromosomes in the GnomAD database, including 139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.023 ( 103 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 36 hom. )

Consequence

PKD1
NM_001009944.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0960

Publications

2 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:

TSC2 (HGNC:12363): (TSC complex subunit 2) This gene is a tumor suppressor gene that encodes the growth inhibitory protein tuberin. Tuberin interacts with hamartin to form the TSC protein complex which functions in the control of cell growth. This TSC protein complex negatively regulates mammalian target of rapamycin complex 1 (mTORC1) signaling which is a major regulator of anabolic cell growth. Mutations in this gene have been associated with tuberous sclerosis and lymphangioleiomyomatosis. [provided by RefSeq, May 2022]

TSC2 Gene-Disease associations (from GenCC):

tuberous sclerosis
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
tuberous sclerosis 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp, Ambry Genetics
lymphangioleiomyomatosis
Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
tuberous sclerosis complex
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

TSC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 16-2088866-C-T is Benign according to our data. Variant chr16-2088866-C-T is described in ClinVar as [Benign]. Clinvar id is 1230996.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1	NM_001009944.3 link	c.*861G>A		3_prime_UTR_variant	Exon 46 of 46	ENST00000262304.9	NP_001009944.3
TSC2	NM_000548.5 link	c.*256C>T		3_prime_UTR_variant	Exon 42 of 42	ENST00000219476.9	NP_000539.2	P49815-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1	ENST00000262304.9 link	c.*861G>A		3_prime_UTR_variant	Exon 46 of 46	1	NM_001009944.3	ENSP00000262304.4		P98161-1
TSC2	ENST00000219476.9 link	c.*256C>T		3_prime_UTR_variant	Exon 42 of 42	5	NM_000548.5	ENSP00000219476.3		P49815-1

Frequencies

GnomAD3 genomes

AF:

0.0227

AC:

2851

AN:

125572

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00827

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00100

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.000110

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000568

Gnomad OTH

AF:

0.0177

GnomAD4 exome

AF:

0.00278

AC:

1056

AN:

379576

Hom.:

Cov.:

AF XY:

0.00223

AC XY:

444

AN XY:

199358

show subpopulations

African (AFR)

AF:

0.0678

AC:

720

AN:

10614

American (AMR)

AF:

0.00620

AC:

AN:

15472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11884

East Asian (EAS)

AF:

0.000229

AC:

AN:

26228

South Asian (SAS)

AF:

0.000114

AC:

AN:

43996

European-Finnish (FIN)

AF:

0.0000445

AC:

AN:

22460

Middle Eastern (MID)

AF:

0.00365

AC:

AN:

1642

European-Non Finnish (NFE)

AF:

0.000350

AC:

AN:

225404

Other (OTH)

AF:

0.00654

AC:

143

AN:

21876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

138

184

230

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0227

AC:

2853

AN:

125626

Hom.:

103

Cov.:

AF XY:

0.0215

AC XY:

1321

AN XY:

61442

show subpopulations

African (AFR)

AF:

0.100

AC:

2673

AN:

26634

American (AMR)

AF:

0.00826

AC:

106

AN:

12836

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3064

East Asian (EAS)

AF:

0.00101

AC:

AN:

4974

South Asian (SAS)

AF:

0.000221

AC:

AN:

4530

European-Finnish (FIN)

AF:

0.000110

AC:

AN:

9108

Middle Eastern (MID)

AF:

0.00

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.000568

AC:

AN:

61586

Other (OTH)

AF:

0.0180

AC:

AN:

1776

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

134

268

402

536

670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0205

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 19, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.9

(source)

DANN

Benign

0.57

PhyloP100

0.096

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Mutation Taster

=100/0

polymorphism

(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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NM_001009944.3:c.*861G>A

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