Variant 3-111072032-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_015480.3(NECTIN3):c.15G>A(p.Leu5Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0262 in 1,533,654 control chromosomes in the GnomAD database, including 3,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 584 hom., cov: 32)

Exomes 𝑓: 0.025 ( 3378 hom. )

Consequence

NECTIN3
NM_015480.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.588

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP6

Variant 3-111072032-G-A is Benign according to our data. Variant chr3-111072032-G-A is described in ClinVar as [Benign]. Clinvar id is 1282802.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.588 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_015480.3 linkuse as main transcript	c.15G>A	p.Leu5Leu	synonymous_variant	1/6	ENST00000485303.6	NP_056295.1	Q9NQS3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000485303.6 linkuse as main transcript	c.15G>A	p.Leu5Leu	synonymous_variant	1/6	1	NM_015480.3	ENSP00000418070.1		Q9NQS3-1

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5758

AN:

151886

Hom.:

578

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00756

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0770

Gnomad ASJ

AF:

0.00518

Gnomad EAS

AF:

0.388

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.00641

Gnomad NFE

AF:

0.00705

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0764

AC:

9927

AN:

129864

Hom.:

1114

AF XY:

0.0702

AC XY:

4931

AN XY:

70246

show subpopulations

Gnomad AFR exome

AF:

0.0134

Gnomad AMR exome

AF:

0.119

Gnomad ASJ exome

AF:

0.00681

Gnomad EAS exome

AF:

0.412

Gnomad SAS exome

AF:

0.0435

Gnomad FIN exome

AF:

0.133

Gnomad NFE exome

AF:

0.00551

Gnomad OTH exome

AF:

0.0454

GnomAD4 exome

AF:

0.0249

AC:

34398

AN:

1381660

Hom.:

3378

Cov.:

AF XY:

0.0251

AC XY:

17100

AN XY:

681264

show subpopulations

Gnomad4 AFR exome

AF:

0.00775

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.00632

Gnomad4 EAS exome

AF:

0.379

Gnomad4 SAS exome

AF:

0.0447

Gnomad4 FIN exome

AF:

0.127

Gnomad4 NFE exome

AF:

0.00526

Gnomad4 OTH exome

AF:

0.0366

GnomAD4 genome

AF:

0.0379

AC:

5768

AN:

151994

Hom.:

584

Cov.:

AF XY:

0.0469

AC XY:

3482

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.00756

Gnomad4 AMR

AF:

0.0780

Gnomad4 ASJ

AF:

0.00518

Gnomad4 EAS

AF:

0.389

Gnomad4 SAS

AF:

0.0539

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.00705

Gnomad4 OTH

AF:

0.0389

Alfa

AF:

0.0129

Hom.:

Bravo

AF:

0.0363

Asia WGS

AF:

0.178

AC:

614

AN:

3464

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 10, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

NECTIN3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 23, 2019

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_noAF

Benign

-0.63

CADD

Benign

7.6

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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