dbSNP rs199504950: PCNX3:p.Glu476Glu (chr11-65618790-G-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_StrongBP6_ModerateBP7

The NM_032223.4(PCNX3):c.1428G>A(p.Glu476Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000383 in 1,611,472 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

PCNX3
NM_032223.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.52

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: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 11-65618790-G-A is Benign according to our data. Variant chr11-65618790-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2641964.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.52 with no splicing effect.

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.1428G>A	p.Glu476Glu	synonymous	Exon 6 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.1428G>A	p.Glu476Glu	synonymous	Exon 6 of 35	ENSP00000347931.3	Q9H6A9-1
PCNX3	ENST00000913358.1		c.1428G>A	p.Glu476Glu	synonymous	Exon 6 of 35	ENSP00000583417.1
PCNX3	ENST00000913354.1		c.1428G>A	p.Glu476Glu	synonymous	Exon 6 of 35	ENSP00000583413.1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00765

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

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:

0.00191

GnomAD2 exomes

AF:

0.000465

AC:

113

AN:

243014

AF XY:

0.000415

show subpopulations

Gnomad AFR exome

AF:

0.00693

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000914

Gnomad OTH exome

AF:

0.000168

GnomAD4 exome

AF:

0.000193

AC:

281

AN:

1459128

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

130

AN XY:

725824

show subpopulations

African (AFR)

AF:

0.00720

AC:

241

AN:

33464

American (AMR)

AF:

0.000314

AC:

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39638

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86124

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51838

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111344

Other (OTH)

AF:

0.000348

AC:

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

102

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:

0.00221

AC:

336

AN:

152344

Hom.:

Cov.:

AF XY:

0.00224

AC XY:

167

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00779

AC:

324

AN:

41576

American (AMR)

AF:

0.000523

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68030

Other (OTH)

AF:

0.00189

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.000680

Hom.:

Bravo

AF:

0.00260

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.7

(source)

DANN

Benign

0.81

PhyloP100

-1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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