Variant 16-71934024-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_181536.2(PKD1L3):c.4715G>A(p.Arg1572His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 1,551,614 control chromosomes in the GnomAD database, including 48,053 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3597 hom., cov: 32)

Exomes 𝑓: 0.25 ( 44456 hom. )

Consequence

PKD1L3
NM_181536.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.106

Variant links:

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]

PKD1L3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003930241).

BP6

Variant 16-71934024-C-T is Benign according to our data. Variant chr16-71934024-C-T is described in ClinVar as [Benign]. Clinvar id is 1221070.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PKD1L3	NM_181536.2 linkuse as main transcript	c.4715G>A	p.Arg1572His	missense_variant	27/30	ENST00000620267.2	NP_853514.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2 linkuse as main transcript	c.4715G>A	p.Arg1572His	missense_variant	27/30	1	NM_181536.2	ENSP00000480090	P1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30136

AN:

152000

Hom.:

3593

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0834

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.0547

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.253

Gnomad MID

AF:

0.218

Gnomad NFE

AF:

0.270

Gnomad OTH

AF:

0.223

GnomAD3 exomes

AF:

0.206

AC:

32454

AN:

157162

Hom.:

3901

AF XY:

0.208

AC XY:

17292

AN XY:

83182

show subpopulations

Gnomad AFR exome

AF:

0.0835

Gnomad AMR exome

AF:

0.141

Gnomad ASJ exome

AF:

0.317

Gnomad EAS exome

AF:

0.0511

Gnomad SAS exome

AF:

0.154

Gnomad FIN exome

AF:

0.235

Gnomad NFE exome

AF:

0.271

Gnomad OTH exome

AF:

0.235

GnomAD4 exome

AF:

0.246

AC:

343692

AN:

1399496

Hom.:

44456

Cov.:

AF XY:

0.244

AC XY:

168397

AN XY:

690240

show subpopulations

Gnomad4 AFR exome

AF:

0.0821

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.0474

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.235

Gnomad4 NFE exome

AF:

0.266

Gnomad4 OTH exome

AF:

0.234

GnomAD4 genome

AF:

0.198

AC:

30159

AN:

152118

Hom.:

3597

Cov.:

AF XY:

0.197

AC XY:

14678

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0839

Gnomad4 AMR

AF:

0.177

Gnomad4 ASJ

AF:

0.329

Gnomad4 EAS

AF:

0.0547

Gnomad4 SAS

AF:

0.161

Gnomad4 FIN

AF:

0.253

Gnomad4 NFE

AF:

0.270

Gnomad4 OTH

AF:

0.220

Alfa

AF:

0.250

Hom.:

8778

Bravo

AF:

0.188

TwinsUK

AF:

0.267

AC:

989

ALSPAC

AF:

0.272

AC:

1050

ESP6500AA

AF:

0.103

AC:

142

ESP6500EA

AF:

0.275

AC:

874

ExAC

AF:

0.191

AC:

4868

Asia WGS

AF:

0.0950

AC:

332

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2019	This variant is associated with the following publications: (PMID: 29083407) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Uncertain

-0.070

CADD

Benign

0.039

DANN

Benign

0.67

DEOGEN2

Benign

0.13

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0039

MutationAssessor

Benign

0.46

PrimateAI

Benign

0.26

Sift4G

Benign

0.34

Polyphen

0.021

Vest4

0.046

GERP RS

-9.4

Varity_R

0.026

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over