NEDD4 p.Ser349Ser

Variant names:

• chr15-55915784-A-A
• ENST00000508342.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr15-55915785--
• chr15-55915785-C-A
• chr15-55915785-C-G
• chr15-55915785-C-T
• chr15-55915785-CGA-ACT
• chr15-55915785-CGA-GCT

Variant summary

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

The NM_198400.3(NEDD4):​c. variant causes a exon region change involving the alteration of a non-conserved nucleotide. 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: 32)
• Consequence: NEDD4 NM_198400.3 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56
• Publications: 0 publications found

Genes affected

NEDD4 (HGNC:7727): (NEDD4 E3 ubiquitin protein ligase) This gene is the founding member of the NEDD4 family of HECT ubiquitin ligases that function in the ubiquitin proteasome system of protein degradation. The encoded protein contains an N-terminal calcium and phospholipid binding C2 domain followed by multiple tryptophan-rich WW domains and, a C-terminal HECT ubiquitin ligase catalytic domain. It plays critical role in the regulation of a number of membrane receptors, endocytic machinery components and the tumor suppressor PTEN. [provided by RefSeq, Jul 2016]

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_198400.3. 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
	NEDD4	NM_006154.4	MANE Select	c.		intron	N/A	NP_006145.2	P46934-4
	NEDD4	NM_001284338.2		c.		exon_region	Exon 1 of 25	NP_001271267.1	P46934-1
	NEDD4	NM_001284339.1		c.		exon_region	Exon 1 of 25	NP_001271268.1	P46934-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NEDD4	ENST00000508342.5	TSL:1	c.		exon_region	Exon 1 of 25	ENSP00000424827.1	P46934-1
	NEDD4	ENST00000506154.1	TSL:1	c.		exon_region	Exon 1 of 25	ENSP00000422705.1	P46934-2
	NEDD4	ENST00000338963.6	TSL:1	c.		exon_region	Exon 1 of 22	ENSP00000345530.2	P46934-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 49

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.6

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: chr15-56207982;