11-119639934-A-T

Variant names:

• chr11-119639934-A-T
• rs7940667
• ENST00000341398.6:n.1082T>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_203285.2(NECTIN1):​c.1082T>A​(p.Val361Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/14 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V361G) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: NECTIN1 NM_203285.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.354

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]

USP2-AS1 (HGNC:48673): (USP2 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33670956).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NECTIN1	NM_203285.2	c.1082T>A	p.Val361Asp	missense_variant	Exon 6 of 8		NP_976030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NECTIN1	ENST00000341398.6	n.1082T>A		non_coding_transcript_exon_variant	Exon 6 of 8	1
NECTIN1	ENST00000531468.2	c.1082T>A	p.Val361Asp	missense_variant	Exon 6 of 10	3		ENSP00000513010.1
USP2-AS1	ENST00000706364.1	n.953A>T		non_coding_transcript_exon_variant	Exon 5 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251242 Hom.: 0 AF XY: 0.00000736 AC XY: 1 AN XY: 135840

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461850 Hom.: 0 Cov.: 64 AF XY: 0.00000275 AC XY: 2 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.0
DANN	Benign	0.76
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.067	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.78	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.20
Sift	Uncertain	0.019	D
Sift4G	Benign	0.092	T
Polyphen		0.40	B
Vest4		0.36
MutPred		0.70		Loss of stability (P = 0.062);
MVP		0.093
ClinPred		0.076	T
GERP RS		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7940667; hg19: chr11-119510644;