Genetic Variant NM_001330177.2:c.1982A>G (chr14-60121235-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001330177.2(PCNX4):c.1982A>G(p.Gln661Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00111 in 1,596,750 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00091 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

PCNX4
NM_001330177.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.71

Publications

4 publications found

Variant links:

Genes affected

PCNX4 (HGNC:20349): (pecanex 4) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

PCNX4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13493302).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330177.2. 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
	PCNX4	NM_001330177.2	MANE Select	c.1982A>G	p.Gln661Arg	missense	Exon 8 of 11	NP_001317106.1	Q63HM2
	PCNX4	NM_022495.5		c.1280A>G	p.Gln427Arg	missense	Exon 7 of 10	NP_071940.4	Q63HM2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCNX4	ENST00000406854.6	TSL:5 MANE Select	c.1982A>G	p.Gln661Arg	missense	Exon 8 of 11	ENSP00000384801.1	Q63HM2
PCNX4	ENST00000868338.1		c.1934A>G	p.Gln645Arg	missense	Exon 8 of 11	ENSP00000538397.1
PCNX4	ENST00000868337.1		c.1562A>G	p.Gln521Arg	missense	Exon 8 of 11	ENSP00000538396.1

Frequencies

GnomAD3 genomes

AF:

0.000908

AC:

128

AN:

140950

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000295

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000536

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000791

AC:

198

AN:

250352

AF XY:

0.000761

show subpopulations

Gnomad AFR exome

AF:

0.000247

Gnomad AMR exome

AF:

0.000695

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.00126

Gnomad OTH exome

AF:

0.000492

GnomAD4 exome

AF:

0.00113

AC:

1644

AN:

1455732

Hom.:

Cov.:

AF XY:

0.00109

AC XY:

793

AN XY:

724250

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33220

American (AMR)

AF:

0.000561

AC:

AN:

44544

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25842

East Asian (EAS)

AF:

0.00

AC:

AN:

39306

South Asian (SAS)

AF:

0.000279

AC:

AN:

86044

European-Finnish (FIN)

AF:

0.000659

AC:

AN:

53130

Middle Eastern (MID)

AF:

0.000175

AC:

AN:

5724

European-Non Finnish (NFE)

AF:

0.00135

AC:

1492

AN:

1107998

Other (OTH)

AF:

0.00105

AC:

AN:

59924

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

182

273

364

455

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

150

200

250

<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:

0.000908

AC:

128

AN:

141018

Hom.:

Cov.:

AF XY:

0.000904

AC XY:

AN XY:

67480

show subpopulations

African (AFR)

AF:

0.000294

AC:

AN:

37406

American (AMR)

AF:

0.000535

AC:

AN:

13072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.00

AC:

AN:

4856

South Asian (SAS)

AF:

0.00

AC:

AN:

4664

European-Finnish (FIN)

AF:

0.00124

AC:

AN:

8044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

240

European-Non Finnish (NFE)

AF:

0.00151

AC:

100

AN:

66444

Other (OTH)

AF:

0.00

AC:

AN:

1934

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:

0.00120

Hom.:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.000782

AC:

EpiCase

AF:

0.00126

EpiControl

AF:

0.000594

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

0.25

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.44

Eigen_PC

Uncertain

0.53

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.029

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

2.9

PhyloP100

8.7

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0050

Polyphen

0.91

Vest4

0.69

MVP

0.35

MPC

0.049

ClinPred

0.089

GERP RS

5.6

Varity_R

0.58

gMVP

0.72

Mutation Taster

=296/4

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