Variant 14-70988600-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_014982.3(PCNX1):c.2345G>A(p.Arg782His) variant causes a missense change. The variant allele was found at a frequency of 0.0037 in 1,614,050 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0038 ( 16 hom. )

Consequence

PCNX1
NM_014982.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.23

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009532601).

BP6

Variant 14-70988600-G-A is Benign according to our data. Variant chr14-70988600-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 787719.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 16 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX1	NM_014982.3 linkuse as main transcript	c.2345G>A	p.Arg782His	missense_variant	7/36	ENST00000304743.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX1	ENST00000304743.7 linkuse as main transcript	c.2345G>A	p.Arg782His	missense_variant	7/36	1	NM_014982.3	P4	Q96RV3-1
PCNX1	ENST00000439984.7 linkuse as main transcript	c.2311+9952G>A		intron_variant		1		A1	Q96RV3-4
PCNX1	ENST00000554879.5 linkuse as main transcript	n.2791G>A		non_coding_transcript_exon_variant	7/10	1
PCNX1	ENST00000556846.1 linkuse as main transcript	n.271+9952G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00234

AC:

356

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00412

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.00208

AC:

522

AN:

251316

Hom.:

AF XY:

0.00207

AC XY:

281

AN XY:

135850

show subpopulations

Gnomad AFR exome

AF:

0.000800

Gnomad AMR exome

AF:

0.000694

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00147

GnomAD4 exome

AF:

0.00384

AC:

5608

AN:

1461824

Hom.:

Cov.:

AF XY:

0.00372

AC XY:

2708

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.000866

Gnomad4 AMR exome

AF:

0.000872

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000267

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.00468

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.00234

AC:

356

AN:

152226

Hom.:

Cov.:

AF XY:

0.00210

AC XY:

156

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00412

Gnomad4 OTH

AF:

0.000475

Alfa

AF:

0.00327

Hom.:

Bravo

AF:

0.00220

TwinsUK

AF:

0.00566

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00453

AC:

ExAC

AF:

0.00202

AC:

245

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00431

EpiControl

AF:

0.00403

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.90

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0095

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-1.0

REVEL

Benign

0.17

Sift

Uncertain

0.0090

Sift4G

Benign

0.11

Polyphen

1.0

Vest4

0.28

MVP

0.082

MPC

0.13

ClinPred

0.018

GERP RS

5.0

Varity_R

0.19

gMVP

0.36

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over