3-111125929-C-T

Position:

• chr3-111125929-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015480.3(NECTIN3):​c.918-255C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0529 in 151,902 control chromosomes in the GnomAD database, including 688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.053 (688 hom., cov: 32)
• Consequence: NECTIN3 NM_015480.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.837

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 3-111125929-C-T is Benign according to our data. Variant chr3-111125929-C-T is described in ClinVar as [Benign]. Clinvar id is 1231758.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_015480.3	c.918-255C>T		intron_variant		ENST00000485303.6	NP_056295.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000485303.6	c.918-255C>T		intron_variant		1	NM_015480.3	ENSP00000418070.1
NECTIN3	ENST00000319792.7	c.918-255C>T		intron_variant		1		ENSP00000321514.3
NECTIN3	ENST00000493615.5	c.849-255C>T		intron_variant		2		ENSP00000420579.1
NECTIN3	ENST00000486596.5	c.618-255C>T		intron_variant		5		ENSP00000417572.1

Frequencies

GnomAD3 genomes AF: 0.0528 AC: 8016 AN: 151784 Hom.: 684 Cov.: 32

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00146

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.000927

Gnomad OTH AF: 0.0412

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

GnomAD4 genome AF: 0.0529 AC: 8038 AN: 151902 Hom.: 688 Cov.: 32 AF XY: 0.0507 AC XY: 3763 AN XY: 74268

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.0192

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00146

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000928

Gnomad4 OTH AF: 0.0408

Alfa AF: 0.0504 Hom.: 84

Bravo AF: 0.0593

Asia WGS AF: 0.00986 AC: 34 AN: 3462

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

Jun 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.41

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: rs1477836; hg19: chr3-110844776;