Genetic Variant PNKD:p.Arg325Ser (chr2-218344559-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015488.5(PNKD):c.973C>A(p.Arg325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R325C) 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

Not reported in ClinVar

Conservation

PhyloP100: 3.52

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 links:

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

CATIP-AS2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19689178).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNKD	NM_015488.5	MANE Select	c.973C>A	p.Arg325Ser	missense	Exon 9 of 10	NP_056303.3
PNKD	NM_022572.4		c.901C>A	p.Arg301Ser	missense	Exon 8 of 9	NP_072094.1	Q8N490-3
CATIP-AS2	NR_125777.1		n.120+6601G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNKD	ENST00000273077.9	TSL:1 MANE Select	c.973C>A	p.Arg325Ser	missense	Exon 9 of 10	ENSP00000273077.4	Q8N490-1
PNKD	ENST00000258362.7	TSL:1	c.901C>A	p.Arg301Ser	missense	Exon 8 of 9	ENSP00000258362.3	Q8N490-3
PNKD	ENST00000685415.1		c.1090C>A	p.Arg364Ser	missense	Exon 10 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1434836

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

711722

African (AFR)

AF:

0.00

AC:

AN:

32902

American (AMR)

AF:

0.00

AC:

AN:

39314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25608

East Asian (EAS)

AF:

0.00

AC:

AN:

38212

South Asian (SAS)

AF:

0.00

AC:

AN:

83522

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51354

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098872

Other (OTH)

AF:

0.00

AC:

AN:

59350

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.24

Eigen

Benign

0.097

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.91

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.20

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

0.48

PhyloP100

3.5

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.8

REVEL

Uncertain

0.45

Sift

Benign

0.50

Sift4G

Benign

0.72

Polyphen

0.68

Vest4

0.31

MVP

0.78

MPC

0.19

ClinPred

0.43

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.30

Mutation Taster

=63/37

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

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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