X-153672654-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001366977.1(PNCK):​c.112G>C​(p.Ala38Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 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)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16950044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PNCK	NM_001366977.1	c.112G>C	p.Ala38Pro	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	c.112G>C	p.Ala38Pro	missense_variant	Exon 3 of 12	5	NM_001366977.1	ENSP00000340586.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	13
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T;.;.;.;T;.;T;T;.;T;T;T
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.71	.;T;T;T;T;T;T;.;.;T;T;.;T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.17	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N;N;N;.;.;.;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N;N;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.076
Sift	Benign	0.090	T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.13	T;T;T;T;T;T;.;.;.;.;.;.;.
Polyphen		0.17	B;B;.;.;P;.;.;.;.;.;.;.;.
Vest4		0.25
MutPred		0.59		Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);.;.;Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);Loss of MoRF binding (P = 0.0679);
MVP		0.64
MPC		1.1
ClinPred		0.36	T
GERP RS		2.1
Varity_R		0.16
gMVP		0.91

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

Other links and lift over

dbSNP: rs144452893; hg19: chrX-152938109;