NM_015488.5:c.559C>A

Variant names:

• chr2-218341568-C-A
• rs375550686
• NM_015488.5:c.559C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.916
• Publications: 0 publications found

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]

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

ACMG classification

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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.559C>A	p.Arg187Arg	synonymous	Exon 6 of 10	NP_056303.3
	PNKD	NM_022572.4		c.487C>A	p.Arg163Arg	synonymous	Exon 5 of 9	NP_072094.1
	CATIP-AS2	NR_125777.1		n.120+9592G>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.559C>A	p.Arg187Arg	synonymous	Exon 6 of 10	ENSP00000273077.4
	PNKD	ENST00000258362.7	TSL:1	c.487C>A	p.Arg163Arg	synonymous	Exon 5 of 9	ENSP00000258362.3
	PNKD	ENST00000685415.1		c.676C>A	p.Arg226Arg	synonymous	Exon 7 of 11	ENSP00000510415.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450320 Hom.: 0 Cov.: 31 AF XY: 0.00000278 AC XY: 2 AN XY: 720212

African (AFR) AF: 0.00 AC: 0 AN: 33258

American (AMR) AF: 0.00 AC: 0 AN: 43792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25840

East Asian (EAS) AF: 0.00 AC: 0 AN: 39138

South Asian (SAS) AF: 0.00 AC: 0 AN: 83942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1106810

Other (OTH) AF: 0.00 AC: 0 AN: 59872

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.18
CADD	Benign	6.2
DANN	Benign	0.91
PhyloP100		0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs375550686; hg19: chr2-219206291;