16-71949873-G-C

Position:

• chr16-71949873-G-C

Variant summary

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

The NM_181536.2(PKD1L3):​c.3528C>G​(p.Ser1176Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.354 in 1,551,090 control chromosomes in the GnomAD database, including 101,518 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.33 (9180 hom., cov: 31)
  • Exomes 𝑓: 0.36 (92338 hom.)
• Consequence: PKD1L3 NM_181536.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.61

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 (MetaRNN=4.4823188E-5).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L3	NM_181536.2	c.3528C>G	p.Ser1176Arg	missense_variant	21/30	ENST00000620267.2	NP_853514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2	c.3528C>G	p.Ser1176Arg	missense_variant	21/30	1	NM_181536.2	ENSP00000480090	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50835 AN: 151762 Hom.: 9179 Cov.: 31

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.450

Gnomad ASJ AF: 0.309

Gnomad EAS AF: 0.662

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.357

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.315

GnomAD3 exomes AF: 0.388 AC: 60690 AN: 156544 Hom.: 13125 AF XY: 0.379 AC XY: 31439 AN XY: 82974

Gnomad AFR exome AF: 0.262

Gnomad AMR exome AF: 0.560

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.674

Gnomad SAS exome AF: 0.314

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.327

Gnomad OTH exome AF: 0.359

GnomAD4 exome AF: 0.356 AC: 498718 AN: 1399212 Hom.: 92338 Cov.: 48 AF XY: 0.355 AC XY: 244673 AN XY: 690108

Gnomad4 AFR exome AF: 0.252

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.615

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.364

Gnomad4 NFE exome AF: 0.348

Gnomad4 OTH exome AF: 0.364

GnomAD4 genome AF: 0.335 AC: 50852 AN: 151878 Hom.: 9180 Cov.: 31 AF XY: 0.338 AC XY: 25079 AN XY: 74216

Gnomad4 AFR AF: 0.261

Gnomad4 AMR AF: 0.450

Gnomad4 ASJ AF: 0.309

Gnomad4 EAS AF: 0.662

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.357

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.313

Alfa AF: 0.322 Hom.: 6121

Bravo AF: 0.345

TwinsUK AF: 0.352 AC: 1307

ALSPAC AF: 0.340 AC: 1309

ESP6500AA AF: 0.259 AC: 358

ESP6500EA AF: 0.333 AC: 1060

ExAC AF: 0.318 AC: 7574

Asia WGS AF: 0.457 AC: 1588 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	23
DANN	Benign	0.81
DEOGEN2	Benign	0.35	T
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.60	T
MetaRNN	Benign	0.000045	T
PrimateAI	Benign	0.38	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.27
GERP RS		3.9
Varity_R		0.23
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1035543; hg19: chr16-71983772; COSMIC: COSV58662084;