rs121434511

Variant names:

• chr2-218270561-C-A
• NM_015488.5:c.26C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-218270561-C-A
• chr2-218270561-C-T

Variant summary

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

The NM_015488.5(PNKD):​c.26C>A​(p.Ala9Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,067,808 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNKD	NM_015488.5	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 10	ENST00000273077.9	NP_056303.3
PNKD	NM_001077399.3	c.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 3		NP_001070867.1
PNKD	XM_017003771.2	c.26C>A	p.Ala9Glu	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.26C>A	p.Ala9Glu	missense_variant	Exon 1 of 10	1	NM_015488.5	ENSP00000273077.4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000187 AC: 2 AN: 1067808 Hom.: 0 Cov.: 18 AF XY: 0.00000391 AC XY: 2 AN XY: 511360

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: 0.00000114

Gnomad4 OTH exome AF: 0.0000232

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.36	D
BayesDel_noAF	Pathogenic	0.28
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;T
Eigen	Uncertain	0.46
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.79	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Uncertain	0.63	D;D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.69	N;N
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.0	N;N
REVEL	Uncertain	0.45
Sift	Uncertain	0.012	D;D
Sift4G	Uncertain	0.042	D;D
Polyphen		1.0	D;D
Vest4		0.73
MutPred		0.38		Gain of catalytic residue at A9 (P = 0.021);Gain of catalytic residue at A9 (P = 0.021);
MVP		0.83
MPC		0.50
ClinPred		0.97	D
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.67
gMVP		0.72

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: chr2-219135284;