Variant X-153674082-A-G 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.94T>C(p.Trp32Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000072 in 1,208,308 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 40 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000089 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.000070 ( 0 hom. 34 hem. )

Consequence

PNCK
NM_001039582.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0710

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.03331074).

BS2

High Hemizygotes in GnomAd at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons
PNCK	NM_001039582.3 linkuse as main transcript	c.94T>C	p.Trp32Arg	missense_variant	1/12
PNCK	NM_001366975.1 linkuse as main transcript	c.-2-1004T>C		intron_variant
PNCK	XM_011531107.3 linkuse as main transcript	c.-2-1004T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	UniProt
PNCK	ENST00000447676.6 linkuse as main transcript	c.94T>C	p.Trp32Arg	missense_variant	1/12	2	Q6P2M8-5
PNCK	ENST00000370142.5 linkuse as main transcript	c.-3+192T>C		intron_variant		5	Q6P2M8-2
PNCK	ENST00000418241.5 linkuse as main transcript	c.-3+550T>C		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000891

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34496

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:

0.000985

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000755

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000116

AC:

AN:

172288

Hom.:

AF XY:

0.0000480

AC XY:

AN XY:

62472

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:

0.000918

Gnomad NFE exome

AF:

0.0000797

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000703

AC:

AN:

1096014

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

362226

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:

0.000787

Gnomad4 NFE exome

AF:

0.0000511

Gnomad4 OTH exome

AF:

0.0000652

GnomAD4 genome

AF:

0.0000891

AC:

AN:

112294

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

34496

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:

0.000985

Gnomad4 NFE

AF:

0.0000755

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ExAC

AF:

0.0000665

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

Jul 09, 2021

The c.94T>C (p.W32R) alteration is located in exon 1 (coding exon 1) of the PNCK gene. This alteration results from a T to C substitution at nucleotide position 94, causing the tryptophan (W) at amino acid position 32 to be replaced by an arginine (R). 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

-0.36

BayesDel_noAF

Benign

-0.57

Cadd

Benign

7.3

Dann

Benign

0.74

FATHMM_MKL

Benign

0.042

LIST_S2

Benign

0.15

M_CAP

Benign

0.057

MetaRNN

Benign

0.033

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-0.32

REVEL

Benign

0.028

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0010

Vest4

0.12

MutPred

0.17

Gain of methylation at W32 (P = 0.064);

MVP

0.82

MPC

1.8

ClinPred

0.13

GERP RS

1.5

gMVP

0.10

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