rs10492825

chr16-71984518-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181536.2(PKD1L3):c.835-351A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,238 control chromosomes in the GnomAD database, including 4,105 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4105 hom., cov: 33)
• Consequence: PKD1L3 NM_181536.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0130

Genes affected

PKD1L3 (HGNC:21716): (polycystin 1 like 3, transient receptor potential channel interacting) This gene encodes a member of the polycystin protein family. The encoded protein contains 11 transmembrane domains, a latrophilin/CL-1-like GPCR proteolytic site (GPS) domain, and a polycystin-1, lipoxygenase, alpha-toxin (PLAT) domain. This protein may function as a component of cation channel pores.[provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PKD1L3	NM_181536.2	c.835-351A>G		intron_variant		ENST00000620267.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PKD1L3	ENST00000620267.2	c.835-351A>G		intron_variant		1	NM_181536.2	P1

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31964 AN: 152120 Hom.: 4104 Cov.: 33

Gnomad AFR AF: 0.0788

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.259

Gnomad OTH AF: 0.223

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.210 AC: 31965 AN: 152238 Hom.: 4105 Cov.: 33 AF XY: 0.212 AC XY: 15755 AN XY: 74426

Gnomad4 AFR AF: 0.0787

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.259

Gnomad4 OTH AF: 0.225

Alfa AF: 0.258 Hom.: 2930

Bravo AF: 0.197

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	7.0
Dann	Benign	0.76

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

LitVar

Other links and lift over

dbSNP: rs10492825; hg19: chr16-72018417;