16-2093862-C-A

Variant names:

• chr16-2093862-C-A
• NM_001009944.3:c.10770G>T
• PKD1 p.Leu3590Leu

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001009944.3(PKD1):​c.10770G>T​(p.Leu3590Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars). Synonymous variant affecting the same amino acid position (i.e. L3590L) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 0 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]

PKD1-AS1 (HGNC:56035): (PKD1 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.177 with no splicing effect.

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.10770G>T	p.Leu3590Leu	synonymous	Exon 36 of 46	NP_001009944.3	P98161-1
	PKD1	NM_000296.4		c.10767G>T	p.Leu3589Leu	synonymous	Exon 36 of 46	NP_000287.4
	PKD1-AS1	NR_135175.1		n.303+850C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.10770G>T	p.Leu3590Leu	synonymous	Exon 36 of 46	ENSP00000262304.4	P98161-1
	PKD1	ENST00000423118.5	TSL:1	c.10767G>T	p.Leu3589Leu	synonymous	Exon 36 of 46	ENSP00000399501.1	P98161-3
	PKD1	ENST00000472659.1	TSL:3	n.207G>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1417342 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 702854

African (AFR) AF: 0.00 AC: 0 AN: 32518

American (AMR) AF: 0.00 AC: 0 AN: 40412

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25556

East Asian (EAS) AF: 0.00 AC: 0 AN: 37536

South Asian (SAS) AF: 0.00 AC: 0 AN: 82154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 38918

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5726

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1095572

Other (OTH) AF: 0.00 AC: 0 AN: 58950

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	0.68
DANN	Benign	0.65
PhyloP100		0.18

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-2143863;