Variant 3-111192402-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_001243288.2(NECTIN3):c.1273C>A(p.Leu425Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000675 in 1,535,546 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0031 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 2 hom. )

Consequence

NECTIN3
NM_001243288.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.70

Variant links:

Genes affected

NECTIN3 (HGNC:17664): (nectin cell adhesion molecule 3) This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

NECTIN3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060964823).

BP6

Variant 3-111192402-C-A is Benign according to our data. Variant chr3-111192402-C-A is described in ClinVar as [Benign]. Clinvar id is 3038574.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NECTIN3	NM_001243288.2 linkuse as main transcript	c.1273C>A	p.Leu425Ile	missense_variant	8/9	NP_001230217.1	Q9NQS3-3
NECTIN3	XM_017006123.2 linkuse as main transcript	c.1435C>A	p.Leu479Ile	missense_variant	9/10	XP_016861612.1
NECTIN3	XM_017006126.2 linkuse as main transcript	c.1342C>A	p.Leu448Ile	missense_variant	8/9	XP_016861615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000493615.5 linkuse as main transcript	c.1273C>A	p.Leu425Ile	missense_variant	8/9	2		ENSP00000420579.1		Q9NQS3-3
NECTIN3	ENST00000485506.1 linkuse as main transcript	c.52C>A	p.Leu18Ile	missense_variant	1/2	2		ENSP00000419829.1		H7C5G5

Frequencies

GnomAD3 genomes

AF:

0.00311

AC:

474

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.000707

AC:

AN:

134308

Hom.:

AF XY:

0.000602

AC XY:

AN XY:

73140

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.000736

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000190

Gnomad OTH exome

AF:

0.000485

GnomAD4 exome

AF:

0.000407

AC:

563

AN:

1383214

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

248

AN XY:

682590

show subpopulations

Gnomad4 AFR exome

AF:

0.0122

Gnomad4 AMR exome

AF:

0.000784

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000816

Gnomad4 OTH exome

AF:

0.000933

GnomAD4 genome

AF:

0.00311

AC:

474

AN:

152332

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

210

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.0105

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00137

Hom.:

Bravo

AF:

0.00345

ExAC

AF:

0.000312

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NECTIN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 10, 2024

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.97

Eigen

Benign

-0.12

Eigen_PC

Benign

0.012

FATHMM_MKL

Benign

0.66

LIST_S2

Benign

0.50

T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-1.0

PROVEAN

Benign

-0.15

N;N

REVEL

Benign

0.013

Sift

Benign

0.29

T;.

Sift4G

Benign

0.63

T;D

Vest4

0.21

MVP

0.18

ClinPred

0.0013

GERP RS

3.5

Splicing

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