rs1553516179

Variant names:

• chr2-218344890-C-T
• rs1553516179
• NM_015488.5:c.1067C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-218344890-C-T
• chr2-218344890-C-A
• chr2-218344890-C-G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_015488.5(PNKD):​c.1067C>T​(p.Pro356Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P356P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: PNKD NM_015488.5 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 6.01
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.093212396).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

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.1067C>T	p.Pro356Leu	missense	Exon 10 of 10	NP_056303.3
	PNKD	NM_022572.4		c.995C>T	p.Pro332Leu	missense	Exon 9 of 9	NP_072094.1	Q8N490-3
	CATIP-AS2	NR_125777.1		n.120+6270G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNKD	ENST00000273077.9	TSL:1 MANE Select	c.1067C>T	p.Pro356Leu	missense	Exon 10 of 10	ENSP00000273077.4	Q8N490-1
	PNKD	ENST00000258362.7	TSL:1	c.995C>T	p.Pro332Leu	missense	Exon 9 of 9	ENSP00000258362.3	Q8N490-3
	PNKD	ENST00000685415.1		c.1184C>T	p.Pro395Leu	missense	Exon 11 of 11	ENSP00000510415.1	A0A8I5KXK0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461578 Hom.: 0 Cov.: 33 AF XY: 0.00000963 AC XY: 7 AN XY: 727124

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1111802

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152174 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74340

African (AFR) AF: 0.0000241 AC: 1 AN: 41442

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)
-	1	-	Paroxysmal nonkinesigenic dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.0040	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Benign	0.87
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.85	D
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.34	T
MutationAssessor	Benign	-1.1	N
PhyloP100		6.0
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.42	N
REVEL	Uncertain	0.32
Sift	Benign	0.47	T
Sift4G	Benign	0.45	T
Polyphen		0.0050	B
Vest4		0.072
MutPred		0.29		Loss of glycosylation at P356 (P = 0.0488)
MVP		0.57
MPC		0.14
ClinPred		0.70	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.035
gMVP		0.15
Mutation Taster		=82/18	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: rs1553516179; hg19: chr2-219209613; COSMIC: COSV51237915; COSMIC: COSV51237915;