rs13332377

Variant names:

• chr16-2088868-C-T
• rs13332377
• NM_001009944.3:c.*859G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-2088868-C-T
• chr16-2088868-C-A
• chr16-2088868-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001009944.3(PKD1):​c.*859G>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 0.129 in 521,830 control chromosomes in the GnomAD database, including 7,701 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4787 hom., cov: 32)
  • Exomes 𝑓: 0.099 (2914 hom.)
• Consequence: PKD1 NM_001009944.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960
• Publications: 9 publications found

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]

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: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics
• lymphangioleiomyomatosis

  Inheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
• tuberous sclerosis complex

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 16-2088868-C-T is Benign according to our data. Variant chr16-2088868-C-T is described in ClinVar as Benign. ClinVar VariationId is 1245044.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001009944.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.*859G>A		3_prime_UTR	Exon 46 of 46	NP_001009944.3	P98161-1
	TSC2	NM_000548.5	MANE Select	c.*258C>T		3_prime_UTR	Exon 42 of 42	NP_000539.2	P49815-1
	PKD1	NM_000296.4		c.*859G>A		3_prime_UTR	Exon 46 of 46	NP_000287.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.*859G>A		3_prime_UTR	Exon 46 of 46	ENSP00000262304.4	P98161-1
	TSC2	ENST00000219476.9	TSL:5 MANE Select	c.*258C>T		3_prime_UTR	Exon 42 of 42	ENSP00000219476.3	P49815-1
	PKD1	ENST00000423118.5	TSL:1	c.*859G>A		3_prime_UTR	Exon 46 of 46	ENSP00000399501.1	P98161-3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 29754 AN: 143528 Hom.: 4776 Cov.: 32

Gnomad AFR AF: 0.469

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.000801

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.217

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.190

GnomAD4 exome AF: 0.0991 AC: 37461 AN: 378198 Hom.: 2914 Cov.: 3 AF XY: 0.0939 AC XY: 18658 AN XY: 198660

African (AFR) AF: 0.435 AC: 4627 AN: 10642

American (AMR) AF: 0.109 AC: 1665 AN: 15330

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 1697 AN: 11822

East Asian (EAS) AF: 0.0000382 AC: 1 AN: 26186

South Asian (SAS) AF: 0.0346 AC: 1519 AN: 43878

European-Finnish (FIN) AF: 0.107 AC: 2407 AN: 22394

Middle Eastern (MID) AF: 0.181 AC: 295 AN: 1628

European-Non Finnish (NFE) AF: 0.101 AC: 22570 AN: 224536

Other (OTH) AF: 0.123 AC: 2680 AN: 21782

GnomAD4 genome AF: 0.207 AC: 29800 AN: 143632 Hom.: 4787 Cov.: 32 AF XY: 0.203 AC XY: 14251 AN XY: 70124

African (AFR) AF: 0.469 AC: 18089 AN: 38560

American (AMR) AF: 0.152 AC: 2157 AN: 14210

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 525 AN: 3324

East Asian (EAS) AF: 0.000803 AC: 4 AN: 4982

South Asian (SAS) AF: 0.0335 AC: 155 AN: 4622

European-Finnish (FIN) AF: 0.129 AC: 1281 AN: 9900

Middle Eastern (MID) AF: 0.230 AC: 65 AN: 282

European-Non Finnish (NFE) AF: 0.109 AC: 7044 AN: 64874

Other (OTH) AF: 0.188 AC: 372 AN: 1978

Alfa AF: 0.134 Hom.: 3168

Bravo AF: 0.214

Asia WGS AF: 0.0420 AC: 147 AN: 3474

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.6
DANN	Benign	0.56
PhyloP100		0.096
RBP_binding_hub_radar		1.1
RBP_regulation_power_radar		2.2
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13332377; hg19: chr16-2138869;