Variant 1-233179093-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP3BP4_StrongBS2

The NM_014801.4(PCNX2):c.3149G>A(p.Arg1050His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000871 in 1,613,758 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 2 hom. )

Consequence

PCNX2
NM_014801.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.87

Variant links:

Genes affected

PCNX2 (HGNC:8736): (pecanex 2) This gene contains coding mononucleotide repeats that are associated with tumors of high mcrosatellite instability (MSI-H). Defects in this gene are involved in the tumorigenesis of MSI-H colorectal carcinomas. [provided by RefSeq, Jun 2016]

PCNX2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 8: BayesDel_noAF, Cadd, Dann, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate, PROVEAN [when BayesDel_addAF, max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.04483214).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCNX2	NM_014801.4 linkuse as main transcript	c.3149G>A	p.Arg1050His	missense_variant	16/34	ENST00000258229.14	NP_055616.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCNX2	ENST00000258229.14 linkuse as main transcript	c.3149G>A	p.Arg1050His	missense_variant	16/34	5	NM_014801.4	ENSP00000258229	A2	A6NKB5-1

Frequencies

GnomAD3 genomes

AF:

0.00104

AC:

159

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000911

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.000735

AC:

183

AN:

249046

Hom.:

AF XY:

0.000681

AC XY:

AN XY:

135116

show subpopulations

Gnomad AFR exome

AF:

0.00103

Gnomad AMR exome

AF:

0.000435

Gnomad ASJ exome

AF:

0.00408

Gnomad EAS exome

AF:

0.0000556

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000833

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.000853

AC:

1246

AN:

1461476

Hom.:

Cov.:

AF XY:

0.000840

AC XY:

611

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.00122

Gnomad4 AMR exome

AF:

0.000358

Gnomad4 ASJ exome

AF:

0.00352

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000896

Gnomad4 OTH exome

AF:

0.000812

GnomAD4 genome

AF:

0.00104

AC:

159

AN:

152282

Hom.:

Cov.:

AF XY:

0.000913

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.00147

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000926

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000982

Hom.:

Bravo

AF:

0.000997

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00121

AC:

ESP6500EA

AF:

0.00106

AC:

ExAC

AF:

0.000776

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000709

EpiControl

AF:

0.00119

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

Aug 28, 2021

The c.3149G>A (p.R1050H) alteration is located in exon 16 (coding exon 16) of the PCNX2 gene. This alteration results from a G to A substitution at nucleotide position 3149, causing the arginine (R) at amino acid position 1050 to be replaced by a histidine (H). 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

Uncertain

0.37

BayesDel_addAF

Benign

-0.014

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.39

T;.;.

Eigen

Pathogenic

0.88

Eigen_PC

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Pathogenic

0.99

D;D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.045

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Pathogenic

3.1

M;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.8

D;D;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

D;D;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.86

MVP

0.73

MPC

0.68

ClinPred

0.11

GERP RS

5.7

Varity_R

0.51

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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