Genetic Variant NM_001366977.1:c.334G>A (chrX-153671960-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001366977.1(PNCK):c.334G>A(p.Asp112Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000645 in 1,209,301 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 24)

Exomes 𝑓: 0.000066 ( 0 hom. 21 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13

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 -4 ACMG points.

BS2

High Hemizygotes in GnomAd4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366977.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNCK	NM_001366977.1	MANE Select	c.334G>A	p.Asp112Asn	missense	Exon 5 of 12	NP_001353906.1	Q6P2M8-1
PNCK	NM_001039582.3		c.583G>A	p.Asp195Asn	missense	Exon 5 of 12	NP_001034671.3	Q6P2M8-5
PNCK	NM_001135740.2		c.385G>A	p.Asp129Asn	missense	Exon 5 of 12	NP_001129212.1	Q6P2M8-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PNCK	ENST00000340888.8	TSL:5 MANE Select	c.334G>A	p.Asp112Asn	missense	Exon 5 of 12	ENSP00000340586.4	Q6P2M8-1
PNCK	ENST00000472324.5	TSL:1	n.553G>A		non_coding_transcript_exon	Exon 4 of 8
PNCK	ENST00000447676.6	TSL:2	c.583G>A	p.Asp195Asn	missense	Exon 5 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes

AF:

0.0000535

AC:

AN:

112224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000648

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000753

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000275

AC:

AN:

181950

AF XY:

0.0000299

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000617

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000656

AC:

AN:

1097077

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

363019

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26373

American (AMR)

AF:

0.00

AC:

AN:

35186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19377

East Asian (EAS)

AF:

0.00

AC:

AN:

30200

South Asian (SAS)

AF:

0.00

AC:

AN:

54070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40429

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3403

European-Non Finnish (NFE)

AF:

0.0000843

AC:

AN:

842034

Other (OTH)

AF:

0.0000217

AC:

AN:

46005

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000535

AC:

AN:

112224

Hom.:

Cov.:

AF XY:

0.0000581

AC XY:

AN XY:

34396

show subpopulations

African (AFR)

AF:

0.0000648

AC:

AN:

30863

American (AMR)

AF:

0.00

AC:

AN:

10723

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2647

East Asian (EAS)

AF:

0.00

AC:

AN:

3556

South Asian (SAS)

AF:

0.00

AC:

AN:

2655

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6212

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000753

AC:

AN:

53131

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000189

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000297

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000218

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.73

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.34

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.20

MetaRNN

Uncertain

0.68

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.1

PhyloP100

6.1

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-4.9

REVEL

Uncertain

0.53

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.90

MVP

0.82

MPC

1.5

ClinPred

0.79

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.74

gMVP

0.91

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over