Genetic Variant NM_001366977.1:c.229G>A (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

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.229G>A	p.Glu77Lys	missense	Exon 4 of 12	NP_001353906.1	Q6P2M8-1
PNCK	NM_001039582.3		c.478G>A	p.Glu160Lys	missense	Exon 4 of 12	NP_001034671.3	Q6P2M8-5
PNCK	NM_001135740.2		c.280G>A	p.Glu94Lys	missense	Exon 4 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.229G>A	p.Glu77Lys	missense	Exon 4 of 12	ENSP00000340586.4	Q6P2M8-1
PNCK	ENST00000472324.5	TSL:1	n.341G>A		non_coding_transcript_exon	Exon 4 of 8
PNCK	ENST00000418241.5	TSL:3	c.249G>A	p.Trp83*	stop_gained	Exon 4 of 4	ENSP00000411267.1	C9J8P0

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

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

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

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.038

MetaRNN

Benign

0.28

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.32

PhyloP100

6.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-2.2

REVEL

Benign

0.27

Sift

Benign

0.61

Sift4G

Benign

0.32

Polyphen

0.019

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over