rs1553654496

Variant names:

• chr2-218270582-G-A
• NM_015488.5:c.47G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218270582-G-A
• chr2-218270582-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_015488.5(PNKD):​c.47G>A​(p.Arg16Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000304 in 987,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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: 33)
  • Exomes 𝑓: 0.0000030 (0 hom.)
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15745074).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.47G>A	p.Arg16Lys	missense_variant	Exon 1 of 10	ENST00000273077.9	NP_056303.3
PNKD	NM_001077399.3	c.47G>A	p.Arg16Lys	missense_variant	Exon 1 of 3		NP_001070867.1
PNKD	XM_017003771.2	c.47G>A	p.Arg16Lys	missense_variant	Exon 1 of 9		XP_016859260.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNKD	ENST00000273077.9	c.47G>A	p.Arg16Lys	missense_variant	Exon 1 of 10	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000304 AC: 3 AN: 987006 Hom.: 0 Cov.: 14 AF XY: 0.00000423 AC XY: 2 AN XY: 473054

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000372

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.095	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Uncertain	0.044	D
MutationAssessor	Benign	0.20	N;N
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.11	N;N
REVEL	Benign	0.15
Sift	Benign	0.14	T;D
Sift4G	Benign	0.75	T;T
Polyphen		0.041	B;B
Vest4		0.24
MutPred		0.30		Gain of ubiquitination at R16 (P = 0.0289);Gain of ubiquitination at R16 (P = 0.0289);
MVP		0.62
MPC		0.16
ClinPred		0.41	T
GERP RS		4.5
Varity_R		0.44
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-219135305;