Variant 14-60125773-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001330177.2(PCNX4):c.3217A>G(p.Ile1073Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,610,998 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 26 hom. )

Consequence

PCNX4
NM_001330177.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.50

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 Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047587156).

BP6

Variant 14-60125773-A-G is Benign according to our data. Variant chr14-60125773-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2644266.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCNX4	NM_001330177.2 linkuse as main transcript	c.3217A>G	p.Ile1073Val	missense_variant	10/11	ENST00000406854.6
PCNX4	NM_022495.5 linkuse as main transcript	c.2515A>G	p.Ile839Val	missense_variant	9/10
PCNX4	XM_047431699.1 linkuse as main transcript	c.3217A>G	p.Ile1073Val	missense_variant	10/11
PCNX4	XM_047431700.1 linkuse as main transcript	c.*113A>G		3_prime_UTR_variant	10/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX4	ENST00000406854.6 linkuse as main transcript	c.3217A>G	p.Ile1073Val	missense_variant	10/11	5	NM_001330177.2	P2

Frequencies

GnomAD3 genomes

AF:

0.00341

AC:

519

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000821

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00590

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00526

GnomAD3 exomes

AF:

0.00367

AC:

909

AN:

247928

Hom.:

AF XY:

0.00388

AC XY:

520

AN XY:

134002

show subpopulations

Gnomad AFR exome

AF:

0.000372

Gnomad AMR exome

AF:

0.00323

Gnomad ASJ exome

AF:

0.00821

Gnomad EAS exome

AF:

0.0000548

Gnomad SAS exome

AF:

0.00407

Gnomad FIN exome

AF:

0.000510

Gnomad NFE exome

AF:

0.00495

Gnomad OTH exome

AF:

0.00364

GnomAD4 exome

AF:

0.00433

AC:

6321

AN:

1458774

Hom.:

Cov.:

AF XY:

0.00431

AC XY:

3125

AN XY:

725568

show subpopulations

Gnomad4 AFR exome

AF:

0.000630

Gnomad4 AMR exome

AF:

0.00280

Gnomad4 ASJ exome

AF:

0.00841

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.00418

Gnomad4 FIN exome

AF:

0.000844

Gnomad4 NFE exome

AF:

0.00478

Gnomad4 OTH exome

AF:

0.00380

GnomAD4 genome

AF:

0.00342

AC:

520

AN:

152224

Hom.:

Cov.:

AF XY:

0.00333

AC XY:

248

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00589

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00456

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00478

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00434

Hom.:

Bravo

AF:

0.00344

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00597

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00442

AC:

ExAC

AF:

0.00358

AC:

434

Asia WGS

AF:

0.00145

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

PCNX4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.5

DANN

Benign

0.45

DEOGEN2

Benign

0.0063

.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.0054

MetaRNN

Benign

0.0048

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.86

.;N;.

MutationTaster

Benign

0.90

N;N;N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

0.19

N;N;N

REVEL

Benign

0.034

Sift

Benign

1.0

T;T;T

Sift4G

Benign

1.0

T;T;T

Polyphen

0.0010, 0.0

.;B;B

Vest4

0.062

MVP

0.055

MPC

0.012

ClinPred

0.00097

GERP RS

-1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.013

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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