X-153670532-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP3 BP6_Moderate BS2

The NM_001366977.1(PNCK):c.957C>T(p.Gly319=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00662 in 1,209,258 control chromosomes in the GnomAD database, including 23 homozygotes. There are 2,478 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (1 hom., 151 hem., cov: 25)
  • Exomes 𝑓: 0.0068 (22 hom. 2327 hem.)
• Consequence: PNCK NM_001366977.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.94

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 -5 ACMG points.

• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• BP6: Variant X-153670532-G-A is Benign according to our data. Variant chrX-153670532-G-A is described in ClinVar as [Benign]. Clinvar id is 782180.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Hemizygotes in GnomAd at 151 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PNCK	NM_001366977.1	c.957C>T	p.Gly319=	synonymous_variant	11/12	ENST00000340888.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PNCK	ENST00000340888.8	c.957C>T	p.Gly319=	synonymous_variant	11/12	5	NM_001366977.1	P1

Frequencies

GnomAD3 genomes AF: 0.00510 AC: 577 AN: 113097 Hom.: 1 Cov.: 25 AF XY: 0.00428 AC XY: 151 AN XY: 35247

Gnomad AFR AF: 0.00103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00185

Gnomad ASJ AF: 0.00525

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000719

Gnomad FIN AF: 0.000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00937

Gnomad OTH AF: 0.00261

GnomAD3 exomes AF: 0.00431 AC: 756 AN: 175469 Hom.: 3 AF XY: 0.00457 AC XY: 285 AN XY: 62389

Gnomad AFR exome AF: 0.000648

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.00358

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00185

Gnomad FIN exome AF: 0.00297

Gnomad NFE exome AF: 0.00745

Gnomad OTH exome AF: 0.00529

GnomAD4 exome AF: 0.00678 AC: 7429 AN: 1096111 Hom.: 22 Cov.: 32 AF XY: 0.00643 AC XY: 2327 AN XY: 362099

Gnomad4 AFR exome AF: 0.000834

Gnomad4 AMR exome AF: 0.00177

Gnomad4 ASJ exome AF: 0.00362

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.00349

Gnomad4 NFE exome AF: 0.00810

Gnomad4 OTH exome AF: 0.00479

GnomAD4 genome AF: 0.00510 AC: 577 AN: 113147 Hom.: 1 Cov.: 25 AF XY: 0.00428 AC XY: 151 AN XY: 35307

Gnomad4 AFR AF: 0.00102

Gnomad4 AMR AF: 0.00184

Gnomad4 ASJ AF: 0.00525

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000721

Gnomad4 FIN AF: 0.000944

Gnomad4 NFE AF: 0.00938

Gnomad4 OTH AF: 0.00258

Alfa AF: 0.00702 Hom.: 62

Bravo AF: 0.00432

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	9.1
Dann	Benign	0.86
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.70		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: rs56246355; hg19: chrX-152935987;