GeneBe

rs142285430

Variant names:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001009944.3(PKD1):​c.*845_*846insTGCG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 0)
Exomes 𝑓: 0.0031 ( 1 hom. )

Consequence

PKD1
NM_001009944.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.365
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00365 (536/146696) while in subpopulation NFE AF= 0.00417 (281/67370). AF 95% confidence interval is 0.00377. There are 1 homozygotes in gnomad4. There are 252 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
BS2
High AC in GnomAd4 at 536 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PKD1NM_001009944.3 linkc.*845_*846insTGCG 3_prime_UTR_variant Exon 46 of 46 ENST00000262304.9 NP_001009944.3
TSC2NM_000548.5 linkc.*272_*273insGCAC 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
PKD1ENST00000262304 linkc.*845_*846insTGCG 3_prime_UTR_variant Exon 46 of 46 1 NM_001009944.3 ENSP00000262304.4 P98161-1
TSC2ENST00000219476.9 linkc.*272_*273insGCAC 3_prime_UTR_variant Exon 42 of 42 5 NM_000548.5 ENSP00000219476.3 P49815-1

Frequencies

GnomAD3 genomes
AF:
0.00365
AC:
535
AN:
146592
Hom.:
1
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00345
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00375
Gnomad ASJ
AF:
0.00409
Gnomad EAS
AF:
0.000976
Gnomad SAS
AF:
0.000418
Gnomad FIN
AF:
0.00425
Gnomad MID
AF:
0.00645
Gnomad NFE
AF:
0.00417
Gnomad OTH
AF:
0.000988
GnomAD4 exome
AF:
0.00306
AC:
839
AN:
274282
Hom.:
1
Cov.:
0
AF XY:
0.00297
AC XY:
430
AN XY:
144962
show subpopulations
Gnomad4 AFR exome
AF:
0.00750
Gnomad4 AMR exome
AF:
0.00179
Gnomad4 ASJ exome
AF:
0.00333
Gnomad4 EAS exome
AF:
0.000801
Gnomad4 SAS exome
AF:
0.000469
Gnomad4 FIN exome
AF:
0.00378
Gnomad4 NFE exome
AF:
0.00360
Gnomad4 OTH exome
AF:
0.00420
GnomAD4 genome
AF:
0.00365
AC:
536
AN:
146696
Hom.:
1
Cov.:
0
AF XY:
0.00351
AC XY:
252
AN XY:
71748
show subpopulations
Gnomad4 AFR
AF:
0.00347
Gnomad4 AMR
AF:
0.00375
Gnomad4 ASJ
AF:
0.00409
Gnomad4 EAS
AF:
0.000978
Gnomad4 SAS
AF:
0.000418
Gnomad4 FIN
AF:
0.00425
Gnomad4 NFE
AF:
0.00417
Gnomad4 OTH
AF:
0.000978

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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.

Other links and lift over

dbSNP: rs142285430; hg19: chr16-2138882; API