dbSNP rs75260332: PCNX3:p.Arg1564Gln (chr11-65634346-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_032223.4(PCNX3):c.4691G>A(p.Arg1564Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,583,496 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 0.00060 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 2 hom. )

Consequence

PCNX3
NM_032223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21

Publications

1 publications found

Variant links:

Genes affected

PCNX3 (HGNC:18760): (pecanex 3) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07323825).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032223.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCNX3	NM_032223.4	MANE Select	c.4691G>A	p.Arg1564Gln	missense	Exon 28 of 35	NP_115599.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCNX3	ENST00000355703.4	TSL:5 MANE Select	c.4691G>A	p.Arg1564Gln	missense	Exon 28 of 35	ENSP00000347931.3	Q9H6A9-1
PCNX3	ENST00000439247.2	TSL:1	n.1363G>A		non_coding_transcript_exon	Exon 8 of 15
PCNX3	ENST00000913358.1		c.4730G>A	p.Arg1577Gln	missense	Exon 28 of 35	ENSP00000583417.1

Frequencies

GnomAD3 genomes

AF:

0.000598

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000109

AC:

AN:

192838

AF XY:

0.0000857

show subpopulations

Gnomad AFR exome

AF:

0.00131

Gnomad AMR exome

AF:

0.000140

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000121

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000615

AC:

AN:

1431162

Hom.:

Cov.:

AF XY:

0.0000536

AC XY:

AN XY:

709446

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

32834

American (AMR)

AF:

0.000224

AC:

AN:

40212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25652

East Asian (EAS)

AF:

0.00

AC:

AN:

38026

South Asian (SAS)

AF:

0.0000363

AC:

AN:

82686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5452

European-Non Finnish (NFE)

AF:

0.0000100

AC:

AN:

1097014

Other (OTH)

AF:

0.000169

AC:

AN:

59158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000604

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.000577

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00214

AC:

AN:

41570

American (AMR)

AF:

0.000131

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000225

Hom.:

Bravo

AF:

0.000672

ESP6500AA

AF:

0.000494

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000101

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.40

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0064

MetaRNN

Benign

0.073

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.6

PhyloP100

9.2

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.17

Sift

Benign

0.12

Sift4G

Benign

0.098

Polyphen

1.0

Vest4

0.57

MVP

0.56

ClinPred

0.11

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.18

gMVP

0.75

Mutation Taster

=88/12

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over