dbSNP rs771612445: PCNX1:p.Gln4His (chr14-70907862-G-C) – 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_014982.3(PCNX1):c.12G>C(p.Gln4His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000468 in 1,281,026 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000047 ( 0 hom. )

Consequence

PCNX1
NM_014982.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.96

Publications

1 publications found

Variant links:

Genes affected

PCNX1 (HGNC:19740): (pecanex 1) This gene encodes an evolutionarily conserved transmembrane protein similar to the pecanex protein in Drosophila. The fly protein is a component of the Notch signaling pathway, which functions in several developmental processes. [provided by RefSeq, Jul 2016]

PCNX1 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=0.3742383).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014982.3. 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
	PCNX1	NM_014982.3	MANE Select	c.12G>C	p.Gln4His	missense	Exon 1 of 36	NP_055797.2	Q96RV3-1
	PCNX1	NM_001308160.2		c.12G>C	p.Gln4His	missense	Exon 1 of 34	NP_001295089.1	Q96RV3-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
PCNX1	ENST00000304743.7	TSL:1 MANE Select	c.12G>C	p.Gln4His	missense	Exon 1 of 36	ENSP00000304192.2	Q96RV3-1
PCNX1	ENST00000439984.7	TSL:1	c.12G>C	p.Gln4His	missense	Exon 1 of 34	ENSP00000396617.3	Q96RV3-4
PCNX1	ENST00000554879.5	TSL:1	n.458G>C		non_coding_transcript_exon	Exon 1 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000778

AC:

AN:

128522

AF XY:

0.0000138

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000167

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000468

AC:

AN:

1281026

Hom.:

Cov.:

AF XY:

0.00000791

AC XY:

AN XY:

631968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26824

American (AMR)

AF:

0.00

AC:

AN:

23096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20836

East Asian (EAS)

AF:

0.00

AC:

AN:

29898

South Asian (SAS)

AF:

0.00

AC:

AN:

59280

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45288

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3702

European-Non Finnish (NFE)

AF:

0.00000588

AC:

AN:

1020690

Other (OTH)

AF:

0.00

AC:

AN:

51412

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

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

Cov.:

ExAC

AF:

0.00000836

AC:

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

Uncertain

0.51

BayesDel_addAF

Uncertain

0.093

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.069

Eigen

Benign

0.17

Eigen_PC

Benign

0.089

FATHMM_MKL

Benign

0.72

LIST_S2

Uncertain

0.93

M_CAP

Pathogenic

0.81

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.74

MutationAssessor

Benign

1.7

PhyloP100

3.0

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.3

REVEL

Benign

0.26

Sift

Benign

0.10

Sift4G

Benign

0.080

Polyphen

0.94

Vest4

0.33

MutPred

0.22

Loss of catalytic residue at Q4 (P = 0.0171)

MVP

0.15

MPC

0.50

ClinPred

0.94

GERP RS

1.8

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.3

Varity_R

0.33

gMVP

0.72

Mutation Taster

=78/22

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

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over