3-111147590-G-A

Position:

• chr3-111147590-G-A

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.1221+106G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 937,724 control chromosomes in the GnomAD database, including 450,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (73279 hom., cov: 32)
  • Exomes 𝑓: 0.98 (377209 hom.)
• Consequence: NECTIN3 NM_001243288.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.44

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=-0.96).
• BP6: Variant 3-111147590-G-A is Benign according to our data. Variant chr3-111147590-G-A is described in ClinVar as [Benign]. Clinvar id is 1231919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NECTIN3	NM_001243288.2	c.1221+106G>A		intron_variant			NP_001230217.1
NECTIN3	XM_017006123.2	c.1383+106G>A		intron_variant			XP_016861612.1
NECTIN3	XM_017006126.2	c.1290+106G>A		intron_variant			XP_016861615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NECTIN3	ENST00000493615.5	c.1221+106G>A		intron_variant		2		ENSP00000420579.1

Frequencies

GnomAD3 genomes AF: 0.981 AC: 149239 AN: 152126 Hom.: 73220 Cov.: 32

Gnomad AFR AF: 0.993

Gnomad AMI AF: 0.977

Gnomad AMR AF: 0.984

Gnomad ASJ AF: 0.967

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.970

Gnomad OTH AF: 0.982

GnomAD4 exome AF: 0.980 AC: 769626 AN: 785480 Hom.: 377209 AF XY: 0.980 AC XY: 392989 AN XY: 400894

Gnomad4 AFR exome AF: 0.994

Gnomad4 AMR exome AF: 0.991

Gnomad4 ASJ exome AF: 0.966

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.996

Gnomad4 FIN exome AF: 0.980

Gnomad4 NFE exome AF: 0.977

Gnomad4 OTH exome AF: 0.980

GnomAD4 genome AF: 0.981 AC: 149357 AN: 152244 Hom.: 73279 Cov.: 32 AF XY: 0.982 AC XY: 73101 AN XY: 74446

Gnomad4 AFR AF: 0.993

Gnomad4 AMR AF: 0.984

Gnomad4 ASJ AF: 0.967

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.986

Gnomad4 NFE AF: 0.970

Gnomad4 OTH AF: 0.982

Alfa AF: 0.976 Hom.: 9136

Bravo AF: 0.982

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.055
DANN	Benign	0.36

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs62273799; hg19: chr3-110866437;