Genetic Variant PKD1L3:p.Thr1232ArgfsTer26 (chr16-71947511-CTTTG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_181536.2(PKD1L3):c.3695_3698delCAAA(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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: 0.794

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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PKD1L3	NM_181536.2 link	c.3695_3698delCAAA	p.Thr1232ArgfsTer26	frameshift_variant	Exon 22 of 30	ENST00000620267.2	NP_853514.1	Q7Z443

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKD1L3	ENST00000620267.2 link	c.3695_3698delCAAA	p.Thr1232ArgfsTer26	frameshift_variant	Exon 22 of 30	1	NM_181536.2	ENSP00000480090.1		Q7Z443

Frequencies

GnomAD3 genomes

AF:

0.274

AC:

41584

AN:

151652

Hom.:

6271

Cov.:

show subpopulations

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

show subpopulations

Gnomad4 AFR exome

AF:

0.401

AC:

12593

AN:

31376

Gnomad4 AMR exome

AF:

0.162

AC:

5788

AN:

35680

Gnomad4 ASJ exome

AF:

0.173

AC:

4353

AN:

25118

Gnomad4 EAS exome

AF:

0.0290

AC:

1034

AN:

35648

Gnomad4 SAS exome

AF:

0.154

AC:

12158

AN:

78978

Gnomad4 FIN exome

AF:

0.207

AC:

10156

AN:

49058

Gnomad4 NFE exome

AF:

0.263

AC:

281265

AN:

1070534

Gnomad4 Remaining exome

AF:

0.232

AC:

13405

AN:

57722

Heterozygous variant carriers

12869

25739

38608

51478

64347

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

9474

18948

28422

37896

47370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.274

AC:

41628

AN:

151772

Hom.:

6283

Cov.:

AF XY:

0.265

AC XY:

19693

AN XY:

74182

show subpopulations

Gnomad4 AFR

AF:

0.395

AC:

0.394658

AN:

0.394658

Gnomad4 AMR

AF:

0.208

AC:

0.208251

AN:

0.208251

Gnomad4 ASJ

AF:

0.188

AC:

0.187572

AN:

0.187572

Gnomad4 EAS

AF:

0.0230

AC:

0.0229907

AN:

0.0229907

Gnomad4 SAS

AF:

0.142

AC:

0.142206

AN:

0.142206

Gnomad4 FIN

AF:

0.191

AC:

0.190697

AN:

0.190697

Gnomad4 NFE

AF:

0.263

AC:

0.262633

AN:

0.262633

Gnomad4 OTH

AF:

0.273

AC:

0.272986

AN:

0.272986

Heterozygous variant carriers

1483

2965

4448

5930

7413

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.148

Hom.:

4049

Bravo

AF:

0.282

ClinVar

Significance: Benign

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Essential tremor

Uncertain:1

University of Washington Center for Mendelian Genomics, University of Washington

Significance:Uncertain significance

Review Status:no assertion criteria provided

Collection Method:research

- -

not provided

Benign:1

Nov 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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