X-153671092-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001366977.1(PNCK):c.713A>G(p.Asp238Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: PNCK NM_001366977.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.745

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNCK	NM_001366977.1	c.713A>G	p.Asp238Gly	missense_variant	8/12	ENST00000340888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNCK	ENST00000340888.8	c.713A>G	p.Asp238Gly	missense_variant	8/12	5	NM_001366977.1	P1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 27, 2023

The c.962A>G (p.D321G) alteration is located in exon 8 (coding exon 8) of the PNCK gene. This alteration results from a A to G substitution at nucleotide position 962, causing the aspartic acid (D) at amino acid position 321 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
Cadd	Uncertain	25
Dann	Uncertain	0.99
DEOGEN2	Benign	0.18	T;T;.;.;.
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.038	D
MetaRNN	Pathogenic	0.75	D;D;D;D;D
MetaSVM	Benign	-0.67	T
MutationAssessor	Benign	-0.44	N;N;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;D
PrimateAI	Uncertain	0.74	T
PROVEAN	Pathogenic	-6.4	D;D;D;D;D
REVEL	Uncertain	0.46
Sift	Uncertain	0.018	D;D;D;D;D
Sift4G	Benign	0.11	T;T;T;T;T
Polyphen		1.0	D;D;.;.;D
Vest4		0.83
MutPred		0.44		Gain of catalytic residue at P234 (P = 0.07);Gain of catalytic residue at P234 (P = 0.07);.;.;.;
MVP		1.0
MPC		0.72
ClinPred		0.97	D
GERP RS		4.3
Varity_R		0.77
gMVP		0.73

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-152936547;