rs34014804

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015488.5(PNKD):c.486G>A(p.Gly162Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0449 in 1,613,360 control chromosomes in the GnomAD database, including 1,975 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 349 hom., cov: 32)

Exomes 𝑓: 0.043 ( 1626 hom. )

Consequence

PNKD
NM_015488.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.49

Variant links:

Genes affected

PNKD (HGNC:9153): (PNKD metallo-beta-lactamase domain containing) This gene is thought to play a role in the regulation of myofibrillogenesis. Mutations in this gene have been associated with the movement disorder paroxysmal non-kinesigenic dyskinesia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

PNKD links:

CATIP-AS2 (HGNC:41079): (CATIP antisense RNA 2)

CATIP-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-218340748-G-A is Benign according to our data. Variant chr2-218340748-G-A is described in ClinVar as [Benign]. Clinvar id is 260662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-218340748-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-2.49 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5 link	c.486G>A	p.Gly162Gly	synonymous_variant	Exon 5 of 10	ENST00000273077.9	NP_056303.3	Q8N490-1A0A024R415

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 link	c.486G>A	p.Gly162Gly	synonymous_variant	Exon 5 of 10	1	NM_015488.5	ENSP00000273077.4		Q8N490-1

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9405

AN:

152008

Hom.:

348

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.0848

Gnomad AMR

AF:

0.0508

Gnomad ASJ

AF:

0.0922

Gnomad EAS

AF:

0.00310

Gnomad SAS

AF:

0.0237

Gnomad FIN

AF:

0.0374

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0470

Gnomad OTH

AF:

0.0618

GnomAD2 exomes

AF:

0.0432

AC:

10863

AN:

251456

AF XY:

0.0426

show subpopulations

Gnomad AFR exome

AF:

0.104

Gnomad AMR exome

AF:

0.0344

Gnomad ASJ exome

AF:

0.0888

Gnomad EAS exome

AF:

0.00234

Gnomad FIN exome

AF:

0.0343

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.0493

GnomAD4 exome

AF:

0.0431

AC:

63009

AN:

1461234

Hom.:

1626

Cov.:

AF XY:

0.0430

AC XY:

31248

AN XY:

726932

show subpopulations

Gnomad4 AFR exome

AF:

0.103

AC:

3438

AN:

33456

Gnomad4 AMR exome

AF:

0.0369

AC:

1650

AN:

44722

Gnomad4 ASJ exome

AF:

0.0881

AC:

2301

AN:

26128

Gnomad4 EAS exome

AF:

0.00131

AC:

AN:

39696

Gnomad4 SAS exome

AF:

0.0240

AC:

2073

AN:

86254

Gnomad4 FIN exome

AF:

0.0322

AC:

1718

AN:

53396

Gnomad4 NFE exome

AF:

0.0438

AC:

48684

AN:

1111440

Gnomad4 Remaining exome

AF:

0.0450

AC:

2718

AN:

60378

Heterozygous variant carriers

3058

6116

9175

12233

15291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

1850

3700

5550

7400

9250

<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:

0.0619

AC:

9416

AN:

152126

Hom.:

349

Cov.:

AF XY:

0.0605

AC XY:

4496

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.105

AC:

0.105398

AN:

0.105398

Gnomad4 AMR

AF:

0.0508

AC:

0.0507598

AN:

0.0507598

Gnomad4 ASJ

AF:

0.0922

AC:

0.0921659

AN:

0.0921659

Gnomad4 EAS

AF:

0.00310

AC:

0.00310438

AN:

0.00310438

Gnomad4 SAS

AF:

0.0241

AC:

0.0240864

AN:

0.0240864

Gnomad4 FIN

AF:

0.0374

AC:

0.0373655

AN:

0.0373655

Gnomad4 NFE

AF:

0.0470

AC:

0.0470239

AN:

0.0470239

Gnomad4 OTH

AF:

0.0607

AC:

0.0607211

AN:

0.0607211

Heterozygous variant carriers

463

927

1390

1854

2317

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<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:

0.0616

Hom.:

289

Bravo

AF:

0.0649

Asia WGS

AF:

0.0270

AC:

AN:

3478

EpiCase

AF:

0.0552

EpiControl

AF:

0.0560

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 25, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 11, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Paroxysmal nonkinesigenic dyskinesia 1

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jun 09, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Paroxysmal nonkinesigenic dyskinesia

Benign:1

Feb 04, 2025

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

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.5

DANN

Benign

0.82

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

polymorphism (auto)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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