Variant X-153671960-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001366977.1(PNCK):c.334G>A(p.Asp112Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,209,301 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000066 ( 0 hom. 21 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNCK	NM_001366977.1 linkuse as main transcript	c.334G>A	p.Asp112Asn	missense_variant	5/12	ENST00000340888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNCK	ENST00000340888.8 linkuse as main transcript	c.334G>A	p.Asp112Asn	missense_variant	5/12	5	NM_001366977.1	P1	Q6P2M8-1

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

112224

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34396

show subpopulations

Gnomad AFR

AF:

0.0000648

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:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000275

AC:

AN:

181950

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

66780

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:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000656

AC:

AN:

1097077

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363019

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:

0.0000843

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.0000535

AC:

AN:

112224

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34396

show subpopulations

Gnomad4 AFR

AF:

0.0000648

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:

0.0000753

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

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 submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.583G>A (p.D195N) alteration is located in exon 5 (coding exon 5) of the PNCK gene. This alteration results from a G to A substitution at nucleotide position 583, causing the aspartic acid (D) at amino acid position 195 to be replaced by an asparagine (N). 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

Pathogenic

0.73

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.16

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

FATHMM_MKL

Pathogenic

0.99

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.68

D;D;D;D;D;D;D

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.1

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

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.9

D;D;D;D;D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

D;D;D;D;D;D;D

Sift4G

Pathogenic

0.0010

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

Polyphen

1.0

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

Vest4

0.90

MVP

0.82

MPC

1.5

ClinPred

0.79

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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