chrX-153672684-C-T

Variant names:

• chrX-153672684-C-T
• rs782249570
• NM_001366977.1:c.82G>A

Variant summary

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

The NM_001366977.1(PNCK):​c.82G>A​(p.Glu28Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000501 in 1,198,028 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000089 (0 hom., 0 hem., cov: 25)
  • Exomes 𝑓: 0.0000046 (0 hom. 4 hem.)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.81
• Publications: 1 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 -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 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.82G>A	p.Glu28Lys	missense	Exon 3 of 12	NP_001353906.1	Q6P2M8-1
	PNCK	NM_001039582.3		c.331G>A	p.Glu111Lys	missense	Exon 3 of 12	NP_001034671.3	Q6P2M8-5
	PNCK	NM_001135740.2		c.133G>A	p.Glu45Lys	missense	Exon 3 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.82G>A	p.Glu28Lys	missense	Exon 3 of 12	ENSP00000340586.4	Q6P2M8-1
	PNCK	ENST00000472324.5	TSL:1	n.194G>A		non_coding_transcript_exon	Exon 3 of 8
	PNCK	ENST00000447676.6	TSL:2	c.331G>A	p.Glu111Lys	missense	Exon 3 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes AF: 0.00000886 AC: 1 AN: 112843 Hom.: 0 Cov.: 25

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000599 AC: 1 AN: 166844 AF XY: 0.0000169

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: 0.0000132

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000461 AC: 5 AN: 1085185 Hom.: 0 Cov.: 32 AF XY: 0.0000112 AC XY: 4 AN XY: 356467

African (AFR) AF: 0.00 AC: 0 AN: 26312

American (AMR) AF: 0.00 AC: 0 AN: 34817

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19095

East Asian (EAS) AF: 0.00 AC: 0 AN: 30075

South Asian (SAS) AF: 0.00 AC: 0 AN: 53640

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32205

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4101

European-Non Finnish (NFE) AF: 0.00000596 AC: 5 AN: 839195

Other (OTH) AF: 0.00 AC: 0 AN: 45745

GnomAD4 genome AF: 0.00000886 AC: 1 AN: 112843 Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0 AN XY: 35029

African (AFR) AF: 0.00 AC: 0 AN: 31078

American (AMR) AF: 0.00 AC: 0 AN: 10836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2654

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2795

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6326

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

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53175

Other (OTH) AF: 0.00 AC: 0 AN: 1520

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.0000165 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	Uncertain	0.37
BayesDel_addAF	Pathogenic	0.16	D
BayesDel_noAF	Uncertain	0.0
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Pathogenic	0.34	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.59	T
MutationAssessor	Benign	-0.095	N
PhyloP100		5.8
PrimateAI	Pathogenic	0.89	D
PROVEAN	Uncertain	-3.3	D
REVEL	Uncertain	0.43
Sift	Benign	0.20	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.59		Gain of MoRF binding (P = 0.0161)
MVP		0.81
MPC		1.2
ClinPred		0.82	D
GERP RS		4.0
PromoterAI		0.0024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.48
gMVP		0.89
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.36		Position offset: -3

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

Other links and lift over

dbSNP: rs782249570; hg19: chrX-152938139; COSMIC: COSV61745363; COSMIC: COSV61745363;