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GeneBe

X-153671301-C-T

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001366977.1(PNCK):c.598G>A(p.Val200Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,208,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.00015 ( 0 hom. 49 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.06
Variant links:
Genes affected
PNCK (HGNC:13415): (pregnancy up-regulated nonubiquitous CaM kinase) PNCK is a member of the calcium/calmodulin-dependent protein kinase family of protein serine/threonine kinases (see CAMK1; MIM 604998) (Gardner et al., 2000 [PubMed 10673339]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.4174637).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PNCKNM_001366977.1 linkuse as main transcriptc.598G>A p.Val200Ile missense_variant 7/12 ENST00000340888.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PNCKENST00000340888.8 linkuse as main transcriptc.598G>A p.Val200Ile missense_variant 7/125 NM_001366977.1 P1Q6P2M8-1

Frequencies

GnomAD3 genomes
AF:
0.0000178
AC:
2
AN:
112046
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34232
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000377
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000333
AC:
6
AN:
180301
Hom.:
0
AF XY:
0.0000153
AC XY:
1
AN XY:
65253
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000748
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000152
AC:
167
AN:
1096192
Hom.:
0
Cov.:
34
AF XY:
0.000135
AC XY:
49
AN XY:
361750
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:
0.000194
Gnomad4 OTH exome
AF:
0.0000869
GnomAD4 genome
AF:
0.0000178
AC:
2
AN:
112046
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34232
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
TwinsUK
AF:
0.000809
AC:
3
ALSPAC
AF:
0.000692
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 02, 2023The c.847G>A (p.V283I) alteration is located in exon 7 (coding exon 7) of the PNCK gene. This alteration results from a G to A substitution at nucleotide position 847, causing the valine (V) at amino acid position 283 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.44
T
BayesDel_noAF
Benign
-0.68
Cadd
Benign
21
Dann
Uncertain
0.99
DEOGEN2
Benign
0.086
T;T;.;.;.;T;.
FATHMM_MKL
Uncertain
0.96
D
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.42
T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.3
L;L;.;.;.;.;.
MutationTaster
Benign
0.98
D;D;D;D;D;D
PrimateAI
Uncertain
0.71
T
PROVEAN
Benign
-0.98
N;N;N;N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.088
T;T;T;T;T;T;T
Sift4G
Benign
0.078
T;T;T;T;T;T;.
Polyphen
0.012
B;B;.;.;B;.;.
Vest4
0.39
MutPred
0.78
Loss of catalytic residue at V200 (P = 0.0095);Loss of catalytic residue at V200 (P = 0.0095);.;.;.;Loss of catalytic residue at V200 (P = 0.0095);Loss of catalytic residue at V200 (P = 0.0095);
MVP
0.77
MPC
0.45
ClinPred
0.18
T
GERP RS
3.1
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.2
Varity_R
0.098
gMVP
0.73

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs782013647; hg19: chrX-152936756; API