Genetic Variant NM_001366977.1:c.866G>A (chrX-153670772-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R289W) has been classified as Uncertain significance.

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

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: Benign. The variant received -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 VariationId is 2341793.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 10 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.866G>A	p.Arg289Gln	missense	Exon 10 of 12	NP_001353906.1	Q6P2M8-1
PNCK	NM_001039582.3		c.1115G>A	p.Arg372Gln	missense	Exon 10 of 12	NP_001034671.3	Q6P2M8-5
PNCK	NM_001135740.2		c.917G>A	p.Arg306Gln	missense	Exon 10 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.866G>A	p.Arg289Gln	missense	Exon 10 of 12	ENSP00000340586.4	Q6P2M8-1
PNCK	ENST00000472324.5	TSL:1	n.1574G>A		non_coding_transcript_exon	Exon 6 of 8
PNCK	ENST00000447676.6	TSL:2	c.1115G>A	p.Arg372Gln	missense	Exon 10 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes

AF:

0.000400

AC:

AN:

112459

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000110

AC:

AN:

182321

AF XY:

0.0000598

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 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

African (AFR)

AF:

0.00106

AC:

AN:

26396

American (AMR)

AF:

0.0000853

AC:

AN:

35159

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19341

East Asian (EAS)

AF:

0.0000331

AC:

AN:

30171

South Asian (SAS)

AF:

0.0000370

AC:

AN:

54011

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40504

Middle Eastern (MID)

AF:

0.000243

AC:

AN:

4118

European-Non Finnish (NFE)

AF:

0.00000238

AC:

AN:

841294

Other (OTH)

AF:

0.000152

AC:

AN:

46026

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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:

0.000400

AC:

AN:

112459

Hom.:

Cov.:

AF XY:

0.000289

AC XY:

AN XY:

34619

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

30918

American (AMR)

AF:

0.0000926

AC:

AN:

10796

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2652

East Asian (EAS)

AF:

0.00

AC:

AN:

3549

South Asian (SAS)

AF:

0.00

AC:

AN:

2740

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6258

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000188

AC:

AN:

53108

Other (OTH)

AF:

0.00

AC:

AN:

1520

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

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:

0.00128

Hom.:

Bravo

AF:

0.000567

ESP6500AA

AF:

0.00130

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000124

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.068

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.028

FATHMM_MKL

Benign

0.066

LIST_S2

Benign

0.77

M_CAP

Benign

0.0059

MetaRNN

Benign

0.019

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

PhyloP100

1.5

PrimateAI

Benign

0.33

PROVEAN

Benign

0.31

REVEL

Benign

0.071

Sift

Benign

0.90

Sift4G

Benign

0.38

Polyphen

0.0

Vest4

0.20

MVP

0.78

MPC

0.63

ClinPred

0.0047

GERP RS

1.8

PromoterAI

-0.11

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.042

gMVP

0.12

Mutation Taster

=99/1

polymorphism

(source)

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

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