NECTIN4 p.Ala7Ala

Variant names:

• chr1-161089275-C-C
• NM_030916.3:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-161089276--
• chr1-161089276-G-A
• chr1-161089276-G-T
• chr1-161089276-G-C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030916.3(NECTIN4):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NECTIN4 NM_030916.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 0 publications found

Genes affected

NECTIN4 (HGNC:19688): (nectin cell adhesion molecule 4) This gene encodes a member of the nectin family. The encoded protein contains two immunoglobulin-like (Ig-like) C2-type domains and one Ig-like V-type domain. It is involved in cell adhesion through trans-homophilic and -heterophilic interactions. It is a single-pass type I membrane protein. The soluble form is produced by proteolytic cleavage at the cell surface by the metalloproteinase ADAM17/TACE. The secreted form is found in both breast tumor cell lines and breast tumor patients. Mutations in this gene are the cause of ectodermal dysplasia-syndactyly syndrome type 1, an autosomal recessive disorder. Alternatively spliced transcript variants have been found but the full-length nature of the variant has not been determined.[provided by RefSeq, Jan 2011]

NECTIN4-AS1 (HGNC:40893): (NECTIN4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030916.3. 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
	NECTIN4	NM_030916.3	MANE Select	c.		exon_region	Exon 1 of 9	NP_112178.2	Q96NY8-1
	NECTIN4-AS1	NR_183640.1		n.		exon_region	Exon 3 of 3
	NECTIN4-AS1	NR_183641.1		n.		exon_region	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NECTIN4	ENST00000368012.4	TSL:1 MANE Select	c.		exon_region	Exon 1 of 9	ENSP00000356991.3	Q96NY8-1
	NECTIN4	ENST00000891630.1		c.		exon_region	Exon 1 of 9	ENSP00000561689.1
	NECTIN4	ENST00000968999.1		c.		exon_region	Exon 2 of 10	ENSP00000639058.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.1

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-161059065;