rs6414248

Variant names:

• chr3-111163479-T-G
• rs6414248
• NM_001243288.2:c.1221+15995T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001243288.2(NECTIN3):​c.1221+15995T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 152,134 control chromosomes in the GnomAD database, including 20,164 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 0.43 (20164 hom., cov: 32)
• Consequence: NECTIN3 NM_001243288.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.446
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN3	NM_001243288.2	c.1221+15995T>G		intron_variant	Intron 7 of 8		NP_001230217.1
NECTIN3	XM_017006123.2	c.1383+15995T>G		intron_variant	Intron 8 of 9		XP_016861612.1
NECTIN3	XM_017006126.2	c.1290+15995T>G		intron_variant	Intron 7 of 8		XP_016861615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000493615.5	c.1221+15995T>G		intron_variant	Intron 7 of 8	2		ENSP00000420579.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65590 AN: 152016 Hom.: 20098 Cov.: 32

Gnomad AFR AF: 0.846

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.432 AC: 65722 AN: 152134 Hom.: 20164 Cov.: 32 AF XY: 0.436 AC XY: 32459 AN XY: 74378

African (AFR) AF: 0.847 AC: 35152 AN: 41514

American (AMR) AF: 0.368 AC: 5626 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1046 AN: 3472

East Asian (EAS) AF: 0.745 AC: 3852 AN: 5170

South Asian (SAS) AF: 0.313 AC: 1508 AN: 4816

European-Finnish (FIN) AF: 0.317 AC: 3364 AN: 10596

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.207 AC: 14076 AN: 67966

Other (OTH) AF: 0.380 AC: 801 AN: 2110

Alfa AF: 0.286 Hom.: 17832

Bravo AF: 0.456

Asia WGS AF: 0.533 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.46
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6414248; hg19: chr3-110882326;