3-111072266-A-G

Position:

• chr3-111072266-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001243288.2(NECTIN3):​c.-154A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.996 in 1,464,612 control chromosomes in the GnomAD database, including 726,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72971 hom., cov: 32)
  • Exomes 𝑓: 1.0 (653558 hom.)
• Consequence: NECTIN3 NM_001243288.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.125

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-111072266-A-G is Benign according to our data. Variant chr3-111072266-A-G is described in ClinVar as [Benign]. Clinvar id is 1263814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_015480.3	c.160+89A>G		intron_variant		ENST00000485303.6	NP_056295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000485303.6	c.160+89A>G		intron_variant		1	NM_015480.3	ENSP00000418070.1

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148839 AN: 152068 Hom.: 72923 Cov.: 32

Gnomad AFR AF: 0.926

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.981

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.987

GnomAD4 exome AF: 0.998 AC: 1309680 AN: 1312434 Hom.: 653558 Cov.: 68 AF XY: 0.998 AC XY: 641152 AN XY: 642304

Gnomad4 AFR exome AF: 0.923

Gnomad4 AMR exome AF: 0.996

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

Gnomad4 OTH exome AF: 0.995

GnomAD4 genome AF: 0.979 AC: 148943 AN: 152178 Hom.: 72971 Cov.: 32 AF XY: 0.980 AC XY: 72876 AN XY: 74378

Gnomad4 AFR AF: 0.926

Gnomad4 AMR AF: 0.993

Gnomad4 ASJ AF: 1.00

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 1.00

Gnomad4 OTH AF: 0.987

Alfa AF: 0.982 Hom.: 10145

Bravo AF: 0.976

Asia WGS AF: 0.997 AC: 3458 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.5
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs4682228; hg19: chr3-110791113;