Variant 3-111133790-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_015480.3(NECTIN3):c.1225G>A(p.Val409Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000507 in 1,613,998 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 Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 0 hom. )

Consequence

NECTIN3
NM_015480.3 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 6.94

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008631349).

BP6

Variant 3-111133790-G-A is Benign according to our data. Variant chr3-111133790-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3035252.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_015480.3 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	6/6	ENST00000485303.6	NP_056295.1	Q9NQS3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NECTIN3	ENST00000485303.6 linkuse as main transcript	c.1225G>A	p.Val409Ile	missense_variant	6/6	1	NM_015480.3	ENSP00000418070.1	Q9NQS3-1
NECTIN3	ENST00000319792.7 linkuse as main transcript	c.*98G>A		3_prime_UTR_variant	6/6	1		ENSP00000321514.3	Q9NQS3-2
NECTIN3	ENST00000493615.5 linkuse as main transcript	c.1000+7455G>A		intron_variant		2		ENSP00000420579.1	Q9NQS3-3

Frequencies

GnomAD3 genomes

AF:

0.000605

AC:

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000662

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000680

AC:

171

AN:

251428

Hom.:

AF XY:

0.000714

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00268

Gnomad NFE exome

AF:

0.000844

Gnomad OTH exome

AF:

0.000815

GnomAD4 exome

AF:

0.000496

AC:

725

AN:

1461746

Hom.:

Cov.:

AF XY:

0.000509

AC XY:

370

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000689

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000359

Gnomad4 FIN exome

AF:

0.00210

Gnomad4 NFE exome

AF:

0.000461

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.000611

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.000658

AC XY:

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.000120

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.000662

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000600

Hom.:

Bravo

AF:

0.000378

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00136

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NECTIN3-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 03, 2023

This variant is classified as likely 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

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.78

M_CAP

Benign

0.0093

MetaRNN

Benign

0.0086

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.55

REVEL

Benign

0.12

Sift

Benign

0.57

Sift4G

Benign

0.39

Polyphen

0.29

Vest4

0.11

MVP

0.11

MPC

0.19

ClinPred

0.050

GERP RS

5.8

Varity_R

0.11

gMVP

0.31

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