NM_001366977.1:c.598G>A

Variant names:

• chrX-153671301-C-T
• rs782013647
• NM_001366977.1:c.598G>A

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001366977.1(PNCK):​c.598G>A​(p.Val200Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00014 in 1,208,238 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 49 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.00015 (0 hom. 49 hem.)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.06
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.4174637).
• BS2: High Hemizygotes in GnomAdExome4 at 49 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNCK	NM_001366977.1	MANE Select	c.598G>A	p.Val200Ile	missense	Exon 7 of 12	NP_001353906.1	Q6P2M8-1
	PNCK	NM_001039582.3		c.847G>A	p.Val283Ile	missense	Exon 7 of 12	NP_001034671.3	Q6P2M8-5
	PNCK	NM_001135740.2		c.649G>A	p.Val217Ile	missense	Exon 7 of 12	NP_001129212.1	Q6P2M8-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PNCK	ENST00000340888.8	TSL:5 MANE Select	c.598G>A	p.Val200Ile	missense	Exon 7 of 12	ENSP00000340586.4	Q6P2M8-1
	PNCK	ENST00000472324.5	TSL:1	n.1212G>A		non_coding_transcript_exon	Exon 4 of 8
	PNCK	ENST00000447676.6	TSL:2	c.847G>A	p.Val283Ile	missense	Exon 7 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes AF: 0.0000178 AC: 2 AN: 112046 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

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: 0.0000377

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000333 AC: 6 AN: 180301 AF XY: 0.0000153

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: 0.0000748

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000152 AC: 167 AN: 1096192 Hom.: 0 Cov.: 34 AF XY: 0.000135 AC XY: 49 AN XY: 361750

African (AFR) AF: 0.00 AC: 0 AN: 26373

American (AMR) AF: 0.00 AC: 0 AN: 35127

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19287

East Asian (EAS) AF: 0.00 AC: 0 AN: 30155

South Asian (SAS) AF: 0.00 AC: 0 AN: 53891

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40437

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4125

European-Non Finnish (NFE) AF: 0.000194 AC: 163 AN: 840789

Other (OTH) AF: 0.0000869 AC: 4 AN: 46008

GnomAD4 genome AF: 0.0000178 AC: 2 AN: 112046 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 34232

African (AFR) AF: 0.00 AC: 0 AN: 30862

American (AMR) AF: 0.00 AC: 0 AN: 10664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2641

East Asian (EAS) AF: 0.00 AC: 0 AN: 3565

South Asian (SAS) AF: 0.00 AC: 0 AN: 2671

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6109

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000377 AC: 2 AN: 53119

Other (OTH) AF: 0.00 AC: 0 AN: 1495

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000692 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.086	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.42	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		6.1
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.11
Sift	Benign	0.088	T
Sift4G	Benign	0.078	T
Polyphen		0.012	B
Vest4		0.39
MutPred		0.78		Loss of catalytic residue at V200 (P = 0.0095)
MVP		0.77
MPC		0.45
ClinPred		0.18	T
GERP RS		3.1
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.098
gMVP		0.73
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs782013647; hg19: chrX-152936756;