Genetic Variant NECTIN1:p.Glu443_Glu444del (chr11-119664967-CCCTCCT-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3

The NM_002855.5(NECTIN1):c.1328_1333delAGGAGG(p.Glu443_Glu444del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000214 in 1,610,502 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

NECTIN1
NM_002855.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.65

Publications

4 publications found

Variant links:

Genes affected

NECTIN1 (HGNC:9706): (nectin cell adhesion molecule 1) This gene encodes an adhesion protein that plays a role in the organization of adherens junctions and tight junctions in epithelial and endothelial cells. The protein is a calcium(2+)-independent cell-cell adhesion molecule that belongs to the immunoglobulin superfamily and has 3 extracellular immunoglobulin-like loops, a single transmembrane domain (in some isoforms), and a cytoplasmic region. This protein acts as a receptor for glycoprotein D (gD) of herpes simplex viruses 1 and 2 (HSV-1, HSV-2), and pseudorabies virus (PRV) and mediates viral entry into epithelial and neuronal cells. Mutations in this gene cause cleft lip and palate/ectodermal dysplasia 1 syndrome (CLPED1) as well as non-syndromic cleft lip with or without cleft palate (CL/P). Alternative splicing results in multiple transcript variants encoding proteins with distinct C-termini. [provided by RefSeq, Oct 2009]

NECTIN1 Gene-Disease associations (from GenCC):

cleft lip/palate-ectodermal dysplasia syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, G2P

NECTIN1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_002855.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002855.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN1	NM_002855.5	MANE Select	c.1328_1333delAGGAGG	p.Glu443_Glu444del	disruptive_inframe_deletion	Exon 6 of 6	NP_002846.3
	NECTIN1	NM_203285.2		c.1003+10186_1003+10191delAGGAGG		intron	N/A	NP_976030.1	Q15223-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NECTIN1	ENST00000264025.8	TSL:1 MANE Select	c.1328_1333delAGGAGG	p.Glu443_Glu444del	disruptive_inframe_deletion	Exon 6 of 6	ENSP00000264025.3	Q15223-1
NECTIN1	ENST00000341398.6	TSL:1	n.1003+10186_1003+10191delAGGAGG		intron	N/A
NECTIN1	ENST00000531468.2	TSL:3	c.1003+10186_1003+10191delAGGAGG		intron	N/A	ENSP00000513010.1	A0A8V8TKI1

Frequencies

GnomAD3 genomes

AF:

0.000277

AC:

AN:

151560

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000194

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00209

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000482

GnomAD2 exomes

AF:

0.000395

AC:

AN:

230564

AF XY:

0.000352

show subpopulations

Gnomad AFR exome

AF:

0.000201

Gnomad AMR exome

AF:

0.0000310

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000172

Gnomad FIN exome

AF:

0.00205

Gnomad NFE exome

AF:

0.000329

Gnomad OTH exome

AF:

0.00158

GnomAD4 exome

AF:

0.000208

AC:

303

AN:

1458942

Hom.:

AF XY:

0.000200

AC XY:

145

AN XY:

725778

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33368

American (AMR)

AF:

0.0000672

AC:

AN:

44648

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26098

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39672

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86184

European-Finnish (FIN)

AF:

0.00235

AC:

125

AN:

53096

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.000125

AC:

139

AN:

1109850

Other (OTH)

AF:

0.000365

AC:

AN:

60268

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000277

AC:

AN:

151560

Hom.:

Cov.:

AF XY:

0.000324

AC XY:

AN XY:

73978

show subpopulations

African (AFR)

AF:

0.000194

AC:

AN:

41284

American (AMR)

AF:

0.00

AC:

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.000208

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.00209

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

67816

Other (OTH)

AF:

0.000482

AC:

AN:

2076

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000204

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.7

Mutation Taster

=170/30

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over