Genetic Variant PKD1L3:p.Asn1228fs (chr16-71947527-TTC-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_181536.2(PKD1L3):c.3681_3682delGA(p.Asn1228fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 1,546,568 control chromosomes in the GnomAD database, including 33 homozygotes. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0081 ( 18 hom., cov: 32)

Exomes 𝑓: 0.00078 ( 15 hom. )

Consequence

PKD1L3
NM_181536.2 frameshift

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.75

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 16-71947527-TTC-T is Benign according to our data. Variant chr16-71947527-TTC-T is described in ClinVar as [Benign]. Clinvar id is 770635.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00807 (1228/152252) while in subpopulation AFR AF = 0.028 (1161/41516). AF 95% confidence interval is 0.0266. There are 18 homozygotes in GnomAd4. There are 562 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 18 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKD1L3	NM_181536.2 link	c.3681_3682delGA	p.Asn1228fs	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.3681_3682delGA	p.Asn1228fs	frameshift_variant	Exon 22 of 30	1	NM_181536.2	ENSP00000480090.1		Q7Z443

Frequencies

GnomAD3 genomes

AF:

0.00805

AC:

1225

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00340

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.000369

AC:

AN:

156978

AF XY:

0.000289

show subpopulations

Gnomad AFR exome

AF:

0.00545

Gnomad AMR exome

AF:

0.000406

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000679

GnomAD4 exome

AF:

0.000781

AC:

1089

AN:

1394316

Hom.:

AF XY:

0.000680

AC XY:

468

AN XY:

688022

show subpopulations

Gnomad4 AFR exome

AF:

0.0280

AC:

882

AN:

31474

Gnomad4 AMR exome

AF:

0.00174

AC:

AN:

35696

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25152

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

35710

Gnomad4 SAS exome

AF:

0.0000885

AC:

AN:

79106

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

49136

Gnomad4 NFE exome

AF:

0.0000130

AC:

AN:

1074466

Gnomad4 Remaining exome

AF:

0.00202

AC:

117

AN:

57882

Heterozygous variant carriers

104

156

208

260

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

128

160

<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:

0.00807

AC:

1228

AN:

152252

Hom.:

Cov.:

AF XY:

0.00755

AC XY:

562

AN XY:

74452

show subpopulations

Gnomad4 AFR

AF:

0.0280

AC:

0.0279651

AN:

0.0279651

Gnomad4 AMR

AF:

0.00340

AC:

0.00340003

AN:

0.00340003

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.0000882

AC:

0.0000882068

AN:

0.0000882068

Gnomad4 OTH

AF:

0.00378

AC:

0.00378072

AN:

0.00378072

Heterozygous variant carriers

117

176

234

293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00360

Hom.:

Bravo

AF:

0.00905

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 29, 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

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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