Genetic Variant PCNX3:p.Ala636Thr (chr11-65619830-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_032223.4(PCNX3):c.1906G>A(p.Ala636Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000295 in 1,605,232 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 0.00026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00030 ( 0 hom. )

Consequence

PCNX3
NM_032223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

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 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=0.23089024).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX3	NM_032223.4 link	c.1906G>A	p.Ala636Thr	missense_variant	Exon 8 of 35	ENST00000355703.4	NP_115599.2	Q9H6A9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCNX3	ENST00000355703.4 link	c.1906G>A	p.Ala636Thr	missense_variant	Exon 8 of 35	5	NM_032223.4	ENSP00000347931.3		Q9H6A9-1
PCNX3	ENST00000531045.1 link	n.-28G>A		upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000500

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000290

AC:

AN:

237550

Hom.:

AF XY:

0.000316

AC XY:

AN XY:

129776

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000147

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.0000673

Gnomad FIN exome

AF:

0.0000567

Gnomad NFE exome

AF:

0.000553

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000299

AC:

434

AN:

1453018

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

233

AN XY:

722594

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000210

Gnomad4 NFE exome

AF:

0.000362

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000263

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000202

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.000958

Alfa

AF:

0.000310

Hom.:

Bravo

AF:

0.000310

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000238

AC:

ExAC

AF:

0.000281

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 18, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1906G>A (p.A636T) alteration is located in exon 8 (coding exon 8) of the PCNX3 gene. This alteration results from a G to A substitution at nucleotide position 1906, causing the alanine (A) at amino acid position 636 to be replaced by a threonine (T). 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

0.46

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.52

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.028

Eigen

Benign

-0.072

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.016

MetaRNN

Benign

0.23

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.55

REVEL

Benign

0.082

Sift

Benign

0.38

Sift4G

Benign

0.46

Polyphen

0.0060

Vest4

0.70

MVP

0.57

ClinPred

0.074

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.055

gMVP

0.43

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