Variant X-153672172-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -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

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 -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 id is 522922.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

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.:

AF XY:

0.0000294

AC XY:

AN XY:

33964

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

GnomAD3 exomes

AF:

0.0000572

AC:

AN:

174940

Hom.:

AF XY:

0.0000332

AC XY:

AN XY:

60294

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 SAS exome

AF:

0.0000592

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

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000696

Gnomad4 SAS exome

AF:

0.0000566

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000131

Gnomad4 OTH exome

AF:

0.0000654

GnomAD4 genome

AF:

0.00000894

AC:

AN:

111807

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34027

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000284

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

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;.;.;.;.;.

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

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