Variant 14-70978353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_014982.3(PCNX1):c.2016G>A(p.Lys672=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,614,142 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.032 ( 221 hom., cov: 31)

Exomes 𝑓: 0.0031 ( 228 hom. )

Consequence

PCNX1
NM_014982.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.25

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 14-70978353-G-A is Benign according to our data. Variant chr14-70978353-G-A is described in ClinVar as [Benign]. Clinvar id is 768660.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.25 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCNX1	NM_014982.3 linkuse as main transcript	c.2016G>A	p.Lys672=	synonymous_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.2016G>A	p.Lys672=	synonymous_variant	6/36	1	NM_014982.3	P4	Q96RV3-1
PCNX1	ENST00000439984.7 linkuse as main transcript	c.2016G>A	p.Lys672=	synonymous_variant	6/34	1		A1	Q96RV3-4
PCNX1	ENST00000554879.5 linkuse as main transcript	n.2462G>A		non_coding_transcript_exon_variant	6/10	1
PCNX1	ENST00000556846.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0315

AC:

4787

AN:

152136

Hom.:

220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0133

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.0321

GnomAD3 exomes

AF:

0.00818

AC:

2057

AN:

251372

Hom.:

AF XY:

0.00569

AC XY:

773

AN XY:

135860

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.00598

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000131

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000123

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00313

AC:

4577

AN:

1461888

Hom.:

228

Cov.:

AF XY:

0.00262

AC XY:

1902

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.110

Gnomad4 AMR exome

AF:

0.00695

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000737

Gnomad4 OTH exome

AF:

0.00775

GnomAD4 genome

AF:

0.0316

AC:

4804

AN:

152254

Hom.:

221

Cov.:

AF XY:

0.0297

AC XY:

2211

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.109

Gnomad4 AMR

AF:

0.0133

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.0318

Alfa

AF:

0.00754

Hom.:

Bravo

AF:

0.0370

Asia WGS

AF:

0.00693

AC:

AN:

3478

EpiCase

AF:

0.000327

EpiControl

AF:

0.000237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

9.6

DANN

Benign

0.84

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