Variant X-153671301-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

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

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]

PNCK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAdExome4 at 49 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNCK	NM_001366977.1 link	c.598G>A	p.Val200Ile	missense_variant	Exon 7 of 12	ENST00000340888.8	NP_001353906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PNCK	ENST00000340888.8 link	c.598G>A	p.Val200Ile	missense_variant	Exon 7 of 12	5	NM_001366977.1	ENSP00000340586.4		Q6P2M8-1

Frequencies

GnomAD3 genomes

AF:

0.0000178

AC:

AN:

112046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

AN:

180301

Hom.:

AF XY:

0.0000153

AC XY:

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.:

Cov.:

AF XY:

0.000135

AC XY:

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:

AN:

112046

Hom.:

Cov.:

AF XY:

0.00

AC XY:

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:

ALSPAC

AF:

0.000692

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 02, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The 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

BayesDel_noAF

Benign

-0.68

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.086

T;T;.;.;.;T;.

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

.;D;D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.42

T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;.;.;.;.;.

PrimateAI

Uncertain

0.71

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over