3-111192236-AG-A

Position:

• chr3-111192236-AG-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001243288.2(NECTIN3):​c.1222-114delG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 894,524 control chromosomes in the GnomAD database, including 917 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (167 hom., cov: 32)
  • Exomes 𝑓: 0.018 (750 hom.)
• Consequence: NECTIN3 NM_001243288.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.221

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 -10 ACMG points.

• BP6: Variant 3-111192236-AG-A is Benign according to our data. Variant chr3-111192236-AG-A is described in ClinVar as [Benign]. Clinvar id is 1240433.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_001243288.2	c.1222-114delG		intron_variant			NP_001230217.1
NECTIN3	XM_017006123.2	c.1384-114delG		intron_variant			XP_016861612.1
NECTIN3	XM_017006126.2	c.1291-114delG		intron_variant			XP_016861615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000493615.5	c.1222-114delG		intron_variant		2		ENSP00000420579.1

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2933 AN: 152182 Hom.: 167 Cov.: 32

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00534

Gnomad OTH AF: 0.0177

GnomAD4 exome AF: 0.0180 AC: 13337 AN: 742224 Hom.: 750 AF XY: 0.0179 AC XY: 6791 AN XY: 379372

Gnomad4 AFR exome AF: 0.00522

Gnomad4 AMR exome AF: 0.00279

Gnomad4 ASJ exome AF: 0.00265

Gnomad4 EAS exome AF: 0.190

Gnomad4 SAS exome AF: 0.0230

Gnomad4 FIN exome AF: 0.0790

Gnomad4 NFE exome AF: 0.00482

Gnomad4 OTH exome AF: 0.0205

GnomAD4 genome AF: 0.0193 AC: 2932 AN: 152300 Hom.: 167 Cov.: 32 AF XY: 0.0250 AC XY: 1864 AN XY: 74464

Gnomad4 AFR AF: 0.00481

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.223

Gnomad4 SAS AF: 0.0311

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.00534

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00569 Hom.: 1

Bravo AF: 0.0139

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs137968265; hg19: chr3-110911083;