X-153672654-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 13/21 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)
• 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: Uncertain_significance. The variant received 0 ACMG points.

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

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>C	p.Ala38Pro	missense	Exon 3 of 12	NP_001353906.1	Q6P2M8-1
	PNCK	NM_001039582.3		c.361G>C	p.Ala121Pro	missense	Exon 3 of 12	NP_001034671.3	Q6P2M8-5
	PNCK	NM_001135740.2		c.163G>C	p.Ala55Pro	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>C	p.Ala38Pro	missense	Exon 3 of 12	ENSP00000340586.4	Q6P2M8-1
	PNCK	ENST00000472324.5	TSL:1	n.224G>C		non_coding_transcript_exon	Exon 3 of 8
	PNCK	ENST00000447676.6	TSL:2	c.361G>C	p.Ala121Pro	missense	Exon 3 of 12	ENSP00000405950.2	Q6P2M8-5

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD2 exomes AF: 0.00 AC: 0 AN: 174401 AF XY: 0.00

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 Cov.: 32

GnomAD4 genome Cov.: 25

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.043	D
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.47	N
PhyloP100		-0.14
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.076
Sift	Benign	0.090	T
Sift4G	Benign	0.13	T
Polyphen		0.17	B
Vest4		0.25
MutPred		0.59		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
Mutation Taster		=86/14	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;