rs1555445526

Variant names:

• chr16-2091492-G-A
• rs1555445526
• NM_001009944.3:c.11643C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-2091492-G-A
• chr16-2091492-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_001009944.3(PKD1):​c.11643C>T​(p.Ala3881Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000024 in 1,247,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000024 (0 hom.)
• Consequence: PKD1 NM_001009944.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.36
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 16-2091492-G-A is Benign according to our data. Variant chr16-2091492-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 447954.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.36 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	NM_001009944.3	MANE Select	c.11643C>T	p.Ala3881Ala	synonymous	Exon 42 of 46	NP_001009944.3
	PKD1	NM_000296.4		c.11640C>T	p.Ala3880Ala	synonymous	Exon 42 of 46	NP_000287.4
	PKD1-AS1	NR_135175.1		n.57G>A		non_coding_transcript_exon	Exon 1 of 3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKD1	ENST00000262304.9	TSL:1 MANE Select	c.11643C>T	p.Ala3881Ala	synonymous	Exon 42 of 46	ENSP00000262304.4
	PKD1	ENST00000423118.5	TSL:1	c.11640C>T	p.Ala3880Ala	synonymous	Exon 42 of 46	ENSP00000399501.1
	PKD1	ENST00000485120.1	TSL:3	n.632C>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000240 AC: 3 AN: 1247858 Hom.: 0 Cov.: 32 AF XY: 0.00000326 AC XY: 2 AN XY: 613404

African (AFR) AF: 0.00 AC: 0 AN: 23024

American (AMR) AF: 0.00 AC: 0 AN: 14346

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18166

East Asian (EAS) AF: 0.00 AC: 0 AN: 26238

South Asian (SAS) AF: 0.00 AC: 0 AN: 64418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31122

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3702

European-Non Finnish (NFE) AF: 0.00000295 AC: 3 AN: 1016502

Other (OTH) AF: 0.00 AC: 0 AN: 50340

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.27
DANN	Benign	0.87
PhyloP100		-1.4

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: rs1555445526; hg19: chr16-2141493;