16-71947511-CTTTG-C

Position:

• chr16-71947511-CTTTG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_181536.2(PKD1L3):​c.3695_3698del​(p.Thr1232ArgfsTer26) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,541,564 control chromosomes in the GnomAD database, including 51,023 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.27 (6283 hom., cov: 19)
  • Exomes 𝑓: 0.25 (44740 hom.)
• Consequence: PKD1L3 NM_181536.2 frameshift
• Clinical Significance: Benign criteria provided, single submitter U:1 B:1
• Conservation: PhyloP100: 0.794

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 -10 ACMG points.

• BP6: Variant 16-71947511-CTTTG-C is Benign according to our data. Variant chr16-71947511-CTTTG-C is described in ClinVar as [Benign]. Clinvar id is 769495.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L3	NM_181536.2	c.3695_3698del	p.Thr1232ArgfsTer26	frameshift_variant	22/30	ENST00000620267.2	NP_853514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2	c.3695_3698del	p.Thr1232ArgfsTer26	frameshift_variant	22/30	1	NM_181536.2	ENSP00000480090	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41584 AN: 151652 Hom.: 6271 Cov.: 19

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.209

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0229

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.246 AC: 342054 AN: 1389792 Hom.: 44740 AF XY: 0.243 AC XY: 166477 AN XY: 686050

Gnomad4 AFR exome AF: 0.401

Gnomad4 AMR exome AF: 0.162

Gnomad4 ASJ exome AF: 0.173

Gnomad4 EAS exome AF: 0.0290

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.207

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.232

GnomAD4 genome AF: 0.274 AC: 41628 AN: 151772 Hom.: 6283 Cov.: 19 AF XY: 0.265 AC XY: 19693 AN XY: 74182

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0230

Gnomad4 SAS AF: 0.142

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.273

Alfa AF: 0.148 Hom.: 4049

Bravo AF: 0.282

ClinVar

Significance: Benign

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Essential tremor Uncertain:1

Uncertain significance, no assertion criteria provided

research

University of Washington Center for Mendelian Genomics, University of Washington

-

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs149635567; hg19: chr16-71981414;