Variant 3-111145008-A-C 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_001243288.2(NECTIN3):c.1110A>C(p.Arg370Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0163 in 1,535,170 control chromosomes in the GnomAD database, including 1,267 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 242 hom., cov: 32)

Exomes 𝑓: 0.015 ( 1025 hom. )

Consequence

NECTIN3
NM_001243288.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0890

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-111145008-A-C is Benign according to our data. Variant chr3-111145008-A-C is described in ClinVar as [Benign]. Clinvar id is 1238252.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.089 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
NECTIN3	NM_001243288.2 linkuse as main transcript	c.1110A>C	p.Arg370Arg	synonymous_variant	6/9	NP_001230217.1	Q9NQS3-3
NECTIN3	XM_017006123.2 linkuse as main transcript	c.1272A>C	p.Arg424Arg	synonymous_variant	7/10	XP_016861612.1
NECTIN3	XM_017006126.2 linkuse as main transcript	c.1179A>C	p.Arg393Arg	synonymous_variant	6/9	XP_016861615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000493615.5 linkuse as main transcript	c.1110A>C	p.Arg370Arg	synonymous_variant	6/9	2		ENSP00000420579.1		Q9NQS3-3

Frequencies

GnomAD3 genomes

AF:

0.0321

AC:

4882

AN:

151880

Hom.:

243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0456

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0121

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.0333

Gnomad FIN

AF:

0.0901

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00587

Gnomad OTH

AF:

0.0259

GnomAD3 exomes

AF:

0.0316

AC:

4300

AN:

135922

Hom.:

354

AF XY:

0.0305

AC XY:

2244

AN XY:

73526

show subpopulations

Gnomad AFR exome

AF:

0.0490

Gnomad AMR exome

AF:

0.00649

Gnomad ASJ exome

AF:

0.00337

Gnomad EAS exome

AF:

0.236

Gnomad SAS exome

AF:

0.0224

Gnomad FIN exome

AF:

0.0783

Gnomad NFE exome

AF:

0.00470

Gnomad OTH exome

AF:

0.0216

GnomAD4 exome

AF:

0.0145

AC:

20060

AN:

1383170

Hom.:

1025

Cov.:

AF XY:

0.0147

AC XY:

10013

AN XY:

682526

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.00247

Gnomad4 EAS exome

AF:

0.203

Gnomad4 SAS exome

AF:

0.0236

Gnomad4 FIN exome

AF:

0.0795

Gnomad4 NFE exome

AF:

0.00459

Gnomad4 OTH exome

AF:

0.0236

GnomAD4 genome

AF:

0.0322

AC:

4889

AN:

152000

Hom.:

242

Cov.:

AF XY:

0.0375

AC XY:

2786

AN XY:

74296

show subpopulations

Gnomad4 AFR

AF:

0.0458

Gnomad4 AMR

AF:

0.0121

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.238

Gnomad4 SAS

AF:

0.0329

Gnomad4 FIN

AF:

0.0901

Gnomad4 NFE

AF:

0.00587

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.00730

Hom.:

Bravo

AF:

0.0281

Asia WGS

AF:

0.105

AC:

366

AN:

3478

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	Nov 12, 2018	- -
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

-0.55

CADD

Benign

4.8

DANN

Benign

0.68

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