Variant X-153672654-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001366977.1(PNCK):c.112G>A(p.Ala38Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000055 in 1,090,682 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 25)

Exomes 𝑓: 0.0000055 ( 0 hom. 2 hem. )

Consequence

PNCK
NM_001366977.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.143

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=0.109766215).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNCK	NM_001366977.1 link	c.112G>A	p.Ala38Thr	missense_variant	Exon 3 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.112G>A	p.Ala38Thr	missense_variant	Exon 3 of 12	5	NM_001366977.1	ENSP00000340586.4		Q6P2M8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000573

AC:

AN:

174401

Hom.:

AF XY:

0.0000158

AC XY:

AN XY:

63415

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 SAS exome

AF:

0.0000532

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000550

AC:

AN:

1090682

Hom.:

Cov.:

AF XY:

0.00000556

AC XY:

AN XY:

359888

show subpopulations

Gnomad4 AFR exome

AF:

0.0000379

Gnomad4 AMR exome

AF:

0.0000285

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000556

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.72

CADD

Benign

8.2

DANN

Benign

0.84

DEOGEN2

Benign

0.043

T;T;.;.;.;T;.;T;T;.;T;T;T

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.62

.;T;T;T;T;T;T;.;.;T;T;.;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.11

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.68

N;N;N;.;.;.;.;.;.;.;.;.;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.6

N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.041

Sift

Benign

0.059

T;T;T;T;D;T;T;T;T;D;D;T;T

Sift4G

Benign

0.15

T;T;T;T;T;T;.;.;.;.;.;.;.

Polyphen

0.0010

B;B;.;.;B;.;.;.;.;.;.;.;.

Vest4

0.058

MutPred

0.50

Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);.;.;Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);Gain of catalytic residue at A38 (P = 0.1307);

MVP

0.60

MPC

0.53

ClinPred

0.26

GERP RS

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.069

gMVP

0.72

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over