rs1477841

Positions:

• chr3-111174420-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243288.2(NECTIN3):​c.1222-17931C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,912 control chromosomes in the GnomAD database, including 12,323 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.29 (12323 hom., cov: 31)
• Consequence: NECTIN3 NM_001243288.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NECTIN3	NM_001243288.2	c.1222-17931C>T		intron_variant
NECTIN3	XM_017006123.2	c.1384-17931C>T		intron_variant
NECTIN3	XM_017006126.2	c.1291-17931C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NECTIN3	ENST00000493615.5	c.1222-17931C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44613 AN: 151794 Hom.: 12283 Cov.: 31

Gnomad AFR AF: 0.708

Gnomad AMI AF: 0.142

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.525

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.262

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.294 AC: 44712 AN: 151912 Hom.: 12323 Cov.: 31 AF XY: 0.297 AC XY: 22070 AN XY: 74232

Gnomad4 AFR AF: 0.708

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.526

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.200

Gnomad4 NFE AF: 0.0731

Gnomad4 OTH AF: 0.259

Alfa AF: 0.109 Hom.: 3181

Bravo AF: 0.320

Asia WGS AF: 0.328 AC: 1140 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.4
DANN	Benign	0.78

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1477841; hg19: chr3-110893267;