Genetic Variant PCNX3:p.Ile2018Val (chr11-65636925-A-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_032223.4(PCNX3):c.6052A>G(p.Ile2018Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000627 in 1,562,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

PCNX3
NM_032223.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.021693707).

BP6

Variant 11-65636925-A-G is Benign according to our data. Variant chr11-65636925-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2399404.Status of the report is criteria_provided_single_submitter, 1 stars.

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.6052A>G	p.Ile2018Val	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.6052A>G	p.Ile2018Val	missense	Exon 35 of 35	ENSP00000347931.3	Q9H6A9-1
PCNX3	ENST00000439247.2	TSL:1	n.2724A>G		non_coding_transcript_exon	Exon 15 of 15
PCNX3	ENST00000913358.1		c.6091A>G	p.Ile2031Val	missense	Exon 35 of 35	ENSP00000583417.1

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000644

AC:

AN:

170872

AF XY:

0.0000547

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000382

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000652

AC:

AN:

1410784

Hom.:

Cov.:

AF XY:

0.0000631

AC XY:

AN XY:

697186

show subpopulations

African (AFR)

AF:

0.0000933

AC:

AN:

32142

American (AMR)

AF:

0.0000538

AC:

AN:

37194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25312

East Asian (EAS)

AF:

0.0000272

AC:

AN:

36734

South Asian (SAS)

AF:

0.0000125

AC:

AN:

80088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.0000764

AC:

AN:

1086060

Other (OTH)

AF:

0.0000342

AC:

AN:

58492

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74408

show subpopulations

African (AFR)

AF:

0.0000723

AC:

AN:

41510

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.000116

Hom.:

Bravo

AF:

0.0000567

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000170

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.050

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.053

(source)

DANN

Benign

0.48

DEOGEN2

Benign

0.011

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0073

LIST_S2

Benign

0.39

M_CAP

Benign

0.0052

MetaRNN

Benign

0.022

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.0

PhyloP100

-1.1

PrimateAI

Benign

0.33

PROVEAN

Benign

0.32

REVEL

Benign

0.021

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.10

MVP

0.26

ClinPred

0.039

GERP RS

0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.012

gMVP

0.032

Mutation Taster

=100/0

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over