X-153670487-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001366977.1(PNCK):c.1002C>T(p.Gly334=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000573 in 1,210,343 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 240 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00040 (0 hom., 13 hem., cov: 25)
  • Exomes 𝑓: 0.00059 (0 hom. 227 hem.)
• Consequence: PNCK NM_001366977.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.597

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant X-153670487-G-A is Benign according to our data. Variant chrX-153670487-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2661706.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNCK	NM_001366977.1	c.1002C>T	p.Gly334=	synonymous_variant	11/12	ENST00000340888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNCK	ENST00000340888.8	c.1002C>T	p.Gly334=	synonymous_variant	11/12	5	NM_001366977.1	P1

Frequencies

GnomAD3 genomes AF: 0.000397 AC: 45 AN: 113395 Hom.: 0 Cov.: 25 AF XY: 0.000366 AC XY: 13 AN XY: 35521

Gnomad AFR AF: 0.0000959

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000184

Gnomad ASJ AF: 0.00451

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000525

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000359 AC: 64 AN: 178079 Hom.: 0 AF XY: 0.000417 AC XY: 27 AN XY: 64715

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000368

Gnomad ASJ exome AF: 0.00245

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000545

Gnomad OTH exome AF: 0.000455

GnomAD4 exome AF: 0.000591 AC: 648 AN: 1096948 Hom.: 0 Cov.: 32 AF XY: 0.000626 AC XY: 227 AN XY: 362776

Gnomad4 AFR exome AF: 0.0000379

Gnomad4 AMR exome AF: 0.0000569

Gnomad4 ASJ exome AF: 0.00279

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000185

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000657

Gnomad4 OTH exome AF: 0.000717

GnomAD4 genome AF: 0.000397 AC: 45 AN: 113395 Hom.: 0 Cov.: 25 AF XY: 0.000366 AC XY: 13 AN XY: 35521

Gnomad4 AFR AF: 0.0000959

Gnomad4 AMR AF: 0.000184

Gnomad4 ASJ AF: 0.00451

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000525

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000304 Hom.: 2

Bravo AF: 0.000336

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

PNCK: BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	13
Dann	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.39		Position offset: 2

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

Publications

LitVar

Other links and lift over

dbSNP: rs149785603; hg19: chrX-152935942;