X-153672654-C-T

Variant names:

• chrX-153672654-C-T
• rs144452893
• NM_001366977.1:c.112G>A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A38S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 25)
  • Exomes 𝑓: 0.0000055 (0 hom. 2 hem.)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 4 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 -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.109766215).
• BS2: High Hemizygotes in GnomAdExome4 at 2 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.112G>A	p.Ala38Thr	missense	Exon 3 of 12	NP_001353906.1	Q6P2M8-1
	PNCK	NM_001039582.3		c.361G>A	p.Ala121Thr	missense	Exon 3 of 12	NP_001034671.3	Q6P2M8-5
	PNCK	NM_001135740.2		c.163G>A	p.Ala55Thr	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.112G>A	p.Ala38Thr	missense	Exon 3 of 12	ENSP00000340586.4	Q6P2M8-1
	PNCK	ENST00000472324.5	TSL:1	n.224G>A		non_coding_transcript_exon	Exon 3 of 8
	PNCK	ENST00000447676.6	TSL:2	c.361G>A	p.Ala121Thr	missense	Exon 3 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00000573 AC: 1 AN: 174401 AF XY: 0.0000158

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000550 AC: 6 AN: 1090682 Hom.: 0 Cov.: 32 AF XY: 0.00000556 AC XY: 2 AN XY: 359888

African (AFR) AF: 0.0000379 AC: 1 AN: 26372

American (AMR) AF: 0.0000285 AC: 1 AN: 35043

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19265

East Asian (EAS) AF: 0.00 AC: 0 AN: 30170

South Asian (SAS) AF: 0.0000556 AC: 3 AN: 53969

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34331

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4119

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841423

Other (OTH) AF: 0.0000217 AC: 1 AN: 45990

GnomAD4 genome Cov.: 25

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	8.2
DANN	Benign	0.84
DEOGEN2	Benign	0.043	T
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.68	N
PhyloP100		-0.14
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.041
Sift	Benign	0.059	T
Sift4G	Benign	0.15	T
Polyphen		0.0010	B
Vest4		0.058
MutPred		0.50		Gain of catalytic residue at A38 (P = 0.1307)
MVP		0.60
MPC		0.53
ClinPred		0.26	T
GERP RS		2.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.069
gMVP		0.72
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs144452893; hg19: chrX-152938109; COSMIC: COSV61743623; COSMIC: COSV61743623;