Variant 14-60121235-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001330177.2(PCNX4):c.1982A>G(p.Gln661Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,596,750 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

PCNX4
NM_001330177.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13493302).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PCNX4	NM_001330177.2 linkuse as main transcript	c.1982A>G	p.Gln661Arg	missense_variant	8/11	ENST00000406854.6
PCNX4	NM_022495.5 linkuse as main transcript	c.1280A>G	p.Gln427Arg	missense_variant	7/10
PCNX4	XM_047431699.1 linkuse as main transcript	c.1982A>G	p.Gln661Arg	missense_variant	8/11
PCNX4	XM_047431700.1 linkuse as main transcript	c.1982A>G	p.Gln661Arg	missense_variant	8/10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX4	ENST00000406854.6 linkuse as main transcript	c.1982A>G	p.Gln661Arg	missense_variant	8/11	5	NM_001330177.2	P2

Frequencies

GnomAD3 genomes

AF:

0.000908

AC:

128

AN:

140950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000791

AC:

198

AN:

250352

Hom.:

AF XY:

0.000761

AC XY:

103

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000295

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.00113

AC:

1644

AN:

1455732

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

793

AN XY:

724250

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000561

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.000659

Gnomad4 NFE exome

AF:

0.00135

Gnomad4 OTH exome

AF:

0.00105

GnomAD4 genome

AF:

0.000908

AC:

128

AN:

141018

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

AN XY:

67480

show subpopulations

Gnomad4 AFR

AF:

0.000294

Gnomad4 AMR

AF:

0.000535

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00124

Gnomad4 NFE

AF:

0.00151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00123

Hom.:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000782

AC:

EpiCase

AF:

0.00126

EpiControl

AF:

0.000594

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

Jul 15, 2021

The c.1280A>G (p.Q427R) alteration is located in exon 7 (coding exon 6) of the PCNX4 gene. This alteration results from a A to G substitution at nucleotide position 1280, causing the glutamine (Q) at amino acid position 427 to be replaced by an arginine (R). 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

Benign

0.25

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

.;T;T

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

D;D;T

M_CAP

Benign

0.029

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

2.9

.;M;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0050

D;D;D

Polyphen

0.91, 0.061

.;P;B

Vest4

0.69

MVP

0.35

MPC

0.049

ClinPred

0.089

GERP RS

5.6

Varity_R

0.58

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