Genetic Variant PCNX3:p.Pro2024Arg (chr11-65636944-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032223.4(PCNX3):c.6071C>G(p.Pro2024Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

PCNX3
NM_032223.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.42

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2683922).

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.6071C>G	p.Pro2024Arg	missense	Exon 35 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.6071C>G	p.Pro2024Arg	missense	Exon 35 of 35	ENSP00000347931.3	Q9H6A9-1
PCNX3	ENST00000439247.2	TSL:1	n.2743C>G		non_coding_transcript_exon	Exon 15 of 15
PCNX3	ENST00000913358.1		c.6110C>G	p.Pro2037Arg	missense	Exon 35 of 35	ENSP00000583417.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000564

AC:

AN:

177268

AF XY:

0.0000105

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000371

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1414954

Hom.:

Cov.:

AF XY:

0.00000143

AC XY:

AN XY:

699790

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32280

American (AMR)

AF:

0.0000264

AC:

AN:

37922

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25392

East Asian (EAS)

AF:

0.00

AC:

AN:

36988

South Asian (SAS)

AF:

0.00

AC:

AN:

80462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1088958

Other (OTH)

AF:

0.00

AC:

AN:

58672

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

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

0.22

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.018

Eigen

Benign

-0.092

Eigen_PC

Benign

-0.16

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

M_CAP

Benign

0.035

MetaRNN

Benign

0.27

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

1.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.52

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.029

Polyphen

0.97

Vest4

0.50

MutPred

0.12

Loss of loop (P = 0.0073)

MVP

0.44

ClinPred

0.44

GERP RS

3.7

Varity_R

0.16

gMVP

0.22

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over