Genetic Variant NM_032223.4:c.2512-83G>A (chr11-65623846-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032223.4(PCNX3):c.2512-83G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 1,591,746 control chromosomes in the GnomAD database, including 49,883 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 5247 hom., cov: 33)

Exomes 𝑓: 0.24 ( 44636 hom. )

Consequence

PCNX3
NM_032223.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.428

Publications

106 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PCNX3	NM_032223.4 link	c.2512-83G>A		intron_variant	Intron 12 of 34	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.2512-83G>A		intron_variant	Intron 12 of 34	5	NM_032223.4	ENSP00000347931.3		Q9H6A9-1

Frequencies

GnomAD3 genomes

AF:

0.254

AC:

38667

AN:

152062

Hom.:

5232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.189

Gnomad AMR

AF:

0.388

Gnomad ASJ

AF:

0.213

Gnomad EAS

AF:

0.415

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.196

Gnomad MID

AF:

0.256

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.237

GnomAD4 exome

AF:

0.241

AC:

346701

AN:

1439564

Hom.:

44636

Cov.:

AF XY:

0.240

AC XY:

171825

AN XY:

717338

show subpopulations

African (AFR)

AF:

0.257

AC:

8496

AN:

33032

American (AMR)

AF:

0.473

AC:

20926

AN:

44272

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

5249

AN:

25922

East Asian (EAS)

AF:

0.472

AC:

18664

AN:

39512

South Asian (SAS)

AF:

0.248

AC:

21263

AN:

85734

European-Finnish (FIN)

AF:

0.205

AC:

10174

AN:

49746

Middle Eastern (MID)

AF:

0.234

AC:

1341

AN:

5720

European-Non Finnish (NFE)

AF:

0.224

AC:

245516

AN:

1095940

Other (OTH)

AF:

0.253

AC:

15072

AN:

59686

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

14018

28036

42054

56072

70090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8690

17380

26070

34760

43450

<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:

0.254

AC:

38717

AN:

152182

Hom.:

5247

Cov.:

AF XY:

0.260

AC XY:

19313

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.259

AC:

10751

AN:

41528

American (AMR)

AF:

0.389

AC:

5945

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

737

AN:

3468

East Asian (EAS)

AF:

0.415

AC:

2146

AN:

5168

South Asian (SAS)

AF:

0.261

AC:

1260

AN:

4830

European-Finnish (FIN)

AF:

0.196

AC:

2079

AN:

10604

Middle Eastern (MID)

AF:

0.252

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15050

AN:

67972

Other (OTH)

AF:

0.238

AC:

503

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1468

2936

4404

5872

7340

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

388

776

1164

1552

1940

<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:

0.241

Hom.:

20550

Bravo

AF:

0.271

Asia WGS

AF:

0.368

AC:

1278

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

6.8

(source)

DANN

Benign

0.83

PhyloP100

0.43

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over