Variant X-153670772-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001366977.1(PNCK):c.866G>A(p.Arg289Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000736 in 1,209,479 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00040 ( 0 hom., 10 hem., cov: 25)

Exomes 𝑓: 0.000040 ( 0 hom. 14 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.55

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01944992).

BP6

Variant X-153670772-C-T is Benign according to our data. Variant chrX-153670772-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2341793.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNCK	NM_001366977.1 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	10/12	ENST00000340888.8	NP_001353906.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNCK	ENST00000340888.8 linkuse as main transcript	c.866G>A	p.Arg289Gln	missense_variant	10/12	5	NM_001366977.1	ENSP00000340586.4		Q6P2M8-1

Frequencies

GnomAD3 genomes

AF:

0.000400

AC:

AN:

112459

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34619

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000926

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:

0.0000188

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

182321

Hom.:

AF XY:

0.0000598

AC XY:

AN XY:

66863

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.0000366

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:

0.0000123

Gnomad OTH exome

AF:

0.000666

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1097020

Hom.:

Cov.:

AF XY:

0.0000386

AC XY:

AN XY:

362508

show subpopulations

Gnomad4 AFR exome

AF:

0.00106

Gnomad4 AMR exome

AF:

0.0000853

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000331

Gnomad4 SAS exome

AF:

0.0000370

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000238

Gnomad4 OTH exome

AF:

0.000152

GnomAD4 genome

AF:

0.000400

AC:

AN:

112459

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34619

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.0000926

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000188

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000689

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000124

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.028

T;T;.;.;.

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.77

.;T;T;T;T

M_CAP

Benign

0.0059

MetaRNN

Benign

0.019

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

N;N;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.31

N;N;N;N;N

REVEL

Benign

0.071

Sift

Benign

0.90

T;T;T;T;T

Sift4G

Benign

0.38

T;T;T;T;T

Polyphen

0.0

B;B;.;.;B

Vest4

0.20

MVP

0.78

MPC

0.63

ClinPred

0.0047

GERP RS

1.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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