dbSNP rs375550686: PNKD:p.Arg187Arg (chr2-218341568-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4BP7

The NM_015488.5(PNKD):c.559C>A(p.Arg187Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,450,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PNKD
NM_015488.5 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.916

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 (BayesDel_noAF=-0.18).

BP7

Synonymous conserved (PhyloP=0.916 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5 link	c.559C>A	p.Arg187Arg	synonymous_variant	Exon 6 of 10	ENST00000273077.9	NP_056303.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9 link	c.559C>A	p.Arg187Arg	synonymous_variant	Exon 6 of 10	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1450320

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

720212

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33258

American (AMR)

AF:

0.00

AC:

AN:

43792

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25840

East Asian (EAS)

AF:

0.00

AC:

AN:

39138

South Asian (SAS)

AF:

0.00

AC:

AN:

83942

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52144

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5524

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1106810

Other (OTH)

AF:

0.00

AC:

AN:

59872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.18

CADD

Benign

6.2

(source)

DANN

Benign

0.91

PhyloP100

0.92

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over