Variant 14-70977749-C-G 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.1412C>G(p.Thr471Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0088 in 1,614,014 control chromosomes in the GnomAD database, including 94 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 31)

Exomes 𝑓: 0.0086 ( 82 hom. )

Consequence

PCNX1
NM_014982.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.832

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=0.0030736625).

BP6

Variant 14-70977749-C-G is Benign according to our data. Variant chr14-70977749-C-G is described in ClinVar as [Benign]. Clinvar id is 788802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX1	NM_014982.3 linkuse as main transcript	c.1412C>G	p.Thr471Ser	missense_variant	6/36	ENST00000304743.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCNX1	ENST00000304743.7 linkuse as main transcript	c.1412C>G	p.Thr471Ser	missense_variant	6/36	1	NM_014982.3	P4	Q96RV3-1
PCNX1	ENST00000439984.7 linkuse as main transcript	c.1412C>G	p.Thr471Ser	missense_variant	6/34	1		A1	Q96RV3-4
PCNX1	ENST00000554879.5 linkuse as main transcript	n.1858C>G		non_coding_transcript_exon_variant	6/10	1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1633

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0141

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0113

Gnomad ASJ

AF:

0.0156

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0170

Gnomad FIN

AF:

0.00226

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00987

Gnomad OTH

AF:

0.0158

GnomAD3 exomes

AF:

0.00908

AC:

2282

AN:

251228

Hom.:

AF XY:

0.00932

AC XY:

1266

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.0156

Gnomad AMR exome

AF:

0.00735

Gnomad ASJ exome

AF:

0.0125

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0150

Gnomad FIN exome

AF:

0.00254

Gnomad NFE exome

AF:

0.00933

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00860

AC:

12569

AN:

1461832

Hom.:

Cov.:

AF XY:

0.00890

AC XY:

6473

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0157

Gnomad4 AMR exome

AF:

0.00801

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0155

Gnomad4 FIN exome

AF:

0.00232

Gnomad4 NFE exome

AF:

0.00833

Gnomad4 OTH exome

AF:

0.00906

GnomAD4 genome

AF:

0.0108

AC:

1636

AN:

152182

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

771

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0141

Gnomad4 AMR

AF:

0.0113

Gnomad4 ASJ

AF:

0.0156

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00226

Gnomad4 NFE

AF:

0.00988

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.0100

Hom.:

Bravo

AF:

0.0116

TwinsUK

AF:

0.00782

AC:

ALSPAC

AF:

0.00752

AC:

ESP6500AA

AF:

0.0132

AC:

ESP6500EA

AF:

0.0100

AC:

ExAC

AF:

0.00927

AC:

1125

Asia WGS

AF:

0.00491

AC:

AN:

3478

EpiCase

AF:

0.0104

EpiControl

AF:

0.0111

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.13

DANN

Benign

0.40

DEOGEN2

Benign

0.014

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.36

T;T

MetaRNN

Benign

0.0031

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.34

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.080

N;N

REVEL

Benign

0.0080

Sift

Benign

0.76

T;T

Sift4G

Benign

0.79

T;T

Polyphen

0.0

B;.

Vest4

0.068

MutPred

0.19

Loss of glycosylation at T471 (P = 0.0966);Loss of glycosylation at T471 (P = 0.0966);

MVP

0.043

MPC

0.092

ClinPred

0.0017

GERP RS

-1.4

Varity_R

0.019

gMVP

0.084

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