Variant X-153674138-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001039582.3(PNCK):c.38G>A(p.Cys13Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,208,589 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000016 ( 0 hom. 10 hem. )

Consequence

PNCK
NM_001039582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.939

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:

PNCK (HGNC:):

PNCK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02176559).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
PNCK	NM_001039582.3 linkuse as main transcript	c.38G>A	p.Cys13Tyr	missense_variant	1/12	NP_001034671.3	Q6P2M8-5
PNCK	NM_001366975.1 linkuse as main transcript	c.-2-1060G>A		intron_variant		NP_001353904.1
PNCK	XM_011531108.3 linkuse as main transcript	c.52+136G>A		intron_variant		XP_011529410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
PNCK	ENST00000447676.6 linkuse as main transcript	c.38G>A	p.Cys13Tyr	missense_variant	1/12	2	ENSP00000405950.2	Q6P2M8-5
PNCK	ENST00000370142.5 linkuse as main transcript	c.-3+136G>A		intron_variant		5	ENSP00000359161.1	Q6P2M8-2
PNCK	ENST00000418241.5 linkuse as main transcript	c.-3+494G>A		intron_variant		3	ENSP00000411267.1	C9J8P0

Frequencies

GnomAD3 genomes

AF:

0.00000886

AC:

AN:

112875

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35007

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:

0.000357

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000513

AC:

AN:

175316

Hom.:

AF XY:

0.0000621

AC XY:

AN XY:

64364

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:

0.000483

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000164

AC:

AN:

1095661

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

361785

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:

0.000297

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

AF:

0.00000886

AC:

AN:

112928

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

35070

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:

0.000358

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000580

AC:

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

Sep 27, 2021

The c.38G>A (p.C13Y) alteration is located in exon 1 (coding exon 1) of the PNCK gene. This alteration results from a G to A substitution at nucleotide position 38, causing the cysteine (C) at amino acid position 13 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.95

DANN

Benign

0.62

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.34

M_CAP

Benign

0.021

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.19

REVEL

Benign

0.031

Sift

Pathogenic

0.0

Polyphen

0.054

Vest4

0.055

MutPred

0.096

Gain of MoRF binding (P = 0.0828);

MVP

0.61

MPC

0.99

ClinPred

0.034

GERP RS

0.56

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

gMVP

0.12

Splicing

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