Genetic Variant PNKD:p.Arg16Ile (chr2-218270582-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015488.5(PNKD):c.47G>T(p.Arg16Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R16G) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PNKD
NM_015488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.08

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

paroxysmal nonkinesigenic dyskinesia 1
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
Tourette syndrome
Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

PNKD links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.47G>T	p.Arg16Ile	missense	Exon 1 of 10	NP_056303.3
	PNKD	NM_001077399.3		c.47G>T	p.Arg16Ile	missense	Exon 1 of 3	NP_001070867.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PNKD	ENST00000273077.9	TSL:1 MANE Select	c.47G>T	p.Arg16Ile	missense	Exon 1 of 10	ENSP00000273077.4
PNKD	ENST00000248451.7	TSL:1	c.47G>T	p.Arg16Ile	missense	Exon 1 of 3	ENSP00000248451.3
PNKD	ENST00000685415.1		c.47G>T	p.Arg16Ile	missense	Exon 1 of 11	ENSP00000510415.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

987006

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

473054

African (AFR)

AF:

0.00

AC:

AN:

21194

American (AMR)

AF:

0.00

AC:

AN:

11456

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13858

East Asian (EAS)

AF:

0.00

AC:

AN:

27216

South Asian (SAS)

AF:

0.00

AC:

AN:

24068

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4344

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

806830

Other (OTH)

AF:

0.00

AC:

AN:

40586

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Paroxysmal nonkinesigenic dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.30

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.34

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.046

MetaRNN

Uncertain

0.48

MetaSVM

Uncertain

0.76

MutationAssessor

Benign

0.55

PhyloP100

2.1

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.36

REVEL

Uncertain

0.38

Sift

Uncertain

0.013

Sift4G

Uncertain

0.042

Polyphen

0.99

Vest4

0.60

MutPred

0.30

Loss of disorder (P = 0.004)

MVP

0.82

MPC

0.39

ClinPred

0.76

GERP RS

4.5

PromoterAI

-0.053

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.33

gMVP

0.39

Mutation Taster

=87/13

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over