dbSNP rs782100269: PNCK:p.Glu77Lys (chrX-153672172-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4BP6BS2

The NM_001366977.1(PNCK):c.229G>A(p.Glu77Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000324 in 1,205,085 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 17 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 1 hem., cov: 24)

Exomes 𝑓: 0.000035 ( 0 hom. 16 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.02

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.284675).

BP6

Variant X-153672172-C-T is Benign according to our data. Variant chrX-153672172-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 522922.

BS2

High Hemizygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNCK	NM_001366977.1 link	c.229G>A	p.Glu77Lys	missense_variant	Exon 4 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.229G>A	p.Glu77Lys	missense_variant	Exon 4 of 12	5	NM_001366977.1	ENSP00000340586.4		Q6P2M8-1

Frequencies

GnomAD3 genomes

AF:

0.00000895

AC:

AN:

111754

Hom.:

Cov.:

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:

0.000283

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000572

AC:

AN:

174940

AF XY:

0.0000332

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000587

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000348

AC:

AN:

1093278

Hom.:

Cov.:

AF XY:

0.0000445

AC XY:

AN XY:

359478

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26323

American (AMR)

AF:

0.00

AC:

AN:

34744

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19010

East Asian (EAS)

AF:

0.000696

AC:

AN:

30165

South Asian (SAS)

AF:

0.0000566

AC:

AN:

52992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40325

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4108

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

839720

Other (OTH)

AF:

0.0000654

AC:

AN:

45891

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111807

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34027

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30779

American (AMR)

AF:

0.00

AC:

AN:

10697

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2643

East Asian (EAS)

AF:

0.000284

AC:

AN:

3523

South Asian (SAS)

AF:

0.00

AC:

AN:

2662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6139

Middle Eastern (MID)

AF:

0.00

AC:

AN:

216

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

52948

Other (OTH)

AF:

0.00

AC:

AN:

1519

Alfa

AF:

0.000118

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 26, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.478G>A (p.E160K) alteration is located in exon 4 (coding exon 4) of the PNCK gene. This alteration results from a G to A substitution at nucleotide position 478, causing the glutamic acid (E) at amino acid position 160 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Benign:1

May 03, 2020

Genomic Research Center, Shahid Beheshti University of Medical Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

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

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.97

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

M_CAP

Benign

0.038

MetaRNN

Benign

0.28

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

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

N;N;N;.;.;.;.;.

PhyloP100

6.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

N;N;N;N;N;N;N;D

REVEL

Benign

0.27

Sift

Benign

0.61

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

Sift4G

Benign

0.32

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

Polyphen

0.019

B;B;.;.;B;.;.;.

Vest4

0.63

MVP

0.83

MPC

1.3

ClinPred

0.15

GERP RS

4.0

Varity_R

0.14

gMVP

0.83

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over