PNKD p.Gly89Arg

Variant names:

• chr2-218339811-G-C
• NM_015488.5:c.265G>C
• PNKD p.Gly89Arg

Your query was ambiguous. Multiple possible variants found:

• chr2-218339811-G-C
• chr2-218339811-G-A
• chr2-218339811-GGG-CGT
• chr2-218339811-GGG-CGC
• chr2-218339811-GGG-CGA
• chr2-218339811-GGG-AGA

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_015488.5(PNKD):​c.265G>C​(p.Gly89Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G89A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.93
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.908

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	NM_015488.5	MANE Select	c.265G>C	p.Gly89Arg	missense	Exon 3 of 10	NP_056303.3
	PNKD	NM_022572.4		c.193G>C	p.Gly65Arg	missense	Exon 2 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+11349C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.265G>C	p.Gly89Arg	missense	Exon 3 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.193G>C	p.Gly65Arg	missense	Exon 2 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.382G>C	p.Gly128Arg	missense	Exon 4 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.66	D
Eigen	Uncertain	0.66
Eigen_PC	Pathogenic	0.70
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	0.34	N
PhyloP100		8.9
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-4.7	D
REVEL	Pathogenic	0.88
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0080	D
Varity_R		0.68
gMVP		0.92
Mutation Taster		=81/19	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-219204534;