2-218340059-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_015488.5(PNKD):​c.383C>G​(p.Ser128Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,400 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S128L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

PNKD
NM_015488.5 missense

Scores

2
15
2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.37
Variant links:
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)

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.76

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PNKDNM_015488.5 linkc.383C>G p.Ser128Trp missense_variant Exon 4 of 10 ENST00000273077.9 NP_056303.3 Q8N490-1A0A024R415

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PNKDENST00000273077.9 linkc.383C>G p.Ser128Trp missense_variant Exon 4 of 10 1 NM_015488.5 ENSP00000273077.4 Q8N490-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460400
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
726584
show subpopulations
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.35
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Uncertain
0.020
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.59
D;.;.
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.52
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Uncertain
0.17
D
MetaRNN
Pathogenic
0.76
D;D;D
MetaSVM
Uncertain
0.21
D
MutationAssessor
Benign
1.6
L;.;.
PrimateAI
Uncertain
0.72
T
PROVEAN
Uncertain
-3.8
D;D;D
REVEL
Uncertain
0.58
Sift
Uncertain
0.0020
D;D;D
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0
D;D;.
Vest4
0.68
MutPred
0.57
Loss of loop (P = 0.0804);.;.;
MVP
0.79
MPC
0.71
ClinPred
0.98
D
GERP RS
3.9
Varity_R
0.48
gMVP
0.86

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: chr2-219204782; API