Variant 3-111126223-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_ModerateBP6BP7BS2_Supporting

The NM_015480.3(NECTIN3):c.957C>T(p.Asp319Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00219 in 1,608,054 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 5 hom. )

Consequence

NECTIN3
NM_015480.3 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.23

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 3-111126223-C-T is Benign according to our data. Variant chr3-111126223-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3038007.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.23 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_015480.3 linkuse as main transcript	c.957C>T	p.Asp319Asp	synonymous_variant	5/6	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.957C>T	p.Asp319Asp	synonymous_variant	5/6	1	NM_015480.3	ENSP00000418070.1	Q9NQS3-1
NECTIN3	ENST00000319792.7 linkuse as main transcript	c.957C>T	p.Asp319Asp	synonymous_variant	5/6	1		ENSP00000321514.3	Q9NQS3-2
NECTIN3	ENST00000493615.5 linkuse as main transcript	c.888C>T	p.Asp296Asp	synonymous_variant	5/9	2		ENSP00000420579.1	Q9NQS3-3
NECTIN3	ENST00000486596.5 linkuse as main transcript	c.657C>T	p.Asp219Asp	synonymous_variant	4/4	5		ENSP00000417572.1	H7C4L0

Frequencies

GnomAD3 genomes

AF:

0.00193

AC:

294

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000507

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00170

AC:

418

AN:

245468

Hom.:

AF XY:

0.00169

AC XY:

224

AN XY:

132896

show subpopulations

Gnomad AFR exome

AF:

0.000518

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.000406

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000235

Gnomad FIN exome

AF:

0.00424

Gnomad NFE exome

AF:

0.00256

Gnomad OTH exome

AF:

0.00235

GnomAD4 exome

AF:

0.00221

AC:

3223

AN:

1455832

Hom.:

Cov.:

AF XY:

0.00213

AC XY:

1541

AN XY:

724146

show subpopulations

Gnomad4 AFR exome

AF:

0.000331

Gnomad4 AMR exome

AF:

0.000273

Gnomad4 ASJ exome

AF:

0.000463

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000234

Gnomad4 FIN exome

AF:

0.00386

Gnomad4 NFE exome

AF:

0.00259

Gnomad4 OTH exome

AF:

0.00145

GnomAD4 genome

AF:

0.00193

AC:

294

AN:

152222

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000505

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00238

Hom.:

Bravo

AF:

0.00136

Asia WGS

AF:

0.000289

AC:

AN:

3474

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

Nov 13, 2019

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

BayesDel_noAF

Benign

-0.41

CADD

Benign

8.6

DANN

Benign

0.46

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