Variant 14-60124427-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001330177.2(PCNX4):c.2256C>G(p.Asn752Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000088 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00031 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

PCNX4
NM_001330177.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.568

Variant links:

Genes affected

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.17644227).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCNX4	NM_001330177.2 linkuse as main transcript	c.2256C>G	p.Asn752Lys	missense_variant	9/11	ENST00000406854.6
PCNX4	NM_022495.5 linkuse as main transcript	c.1554C>G	p.Asn518Lys	missense_variant	8/10
PCNX4	XM_047431699.1 linkuse as main transcript	c.2256C>G	p.Asn752Lys	missense_variant	9/11
PCNX4	XM_047431700.1 linkuse as main transcript	c.2139+117C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX4	ENST00000406854.6 linkuse as main transcript	c.2256C>G	p.Asn752Lys	missense_variant	9/11	5	NM_001330177.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000302

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000846

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000116

AC:

AN:

250366

Hom.:

AF XY:

0.000103

AC XY:

AN XY:

135296

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.0000871

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000708

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1461348

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000134

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000309

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.000867

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.0000547

Hom.:

Bravo

AF:

0.000363

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000123

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2021

The c.1554C>G (p.N518K) alteration is located in exon 8 (coding exon 7) of the PCNX4 gene. This alteration results from a C to G substitution at nucleotide position 1554, causing the asparagine (N) at amino acid position 518 to be replaced by a lysine (K). 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

Pathogenic

0.68

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.10

.;T;T

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.18

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.8

.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.12

Sift

Uncertain

0.0080

D;D;D

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.97, 0.96

.;D;D

Vest4

0.74

MutPred

0.32

.;Gain of ubiquitination at N752 (P = 0.0337);.;

MVP

0.16

MPC

0.030

ClinPred

0.12

GERP RS

0.11

Varity_R

0.24

gMVP

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over