chr15-55850627-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_006154.4(NEDD4):c.1262G>T(p.Gly421Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000308 in 1,461,860 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000031 ( 1 hom. )
Consequence
NEDD4
NM_006154.4 missense
NM_006154.4 missense
Scores
1
5
11
Clinical Significance
Conservation
PhyloP100: 6.01
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]
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ACMG classification
Classification made for transcript
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=0.29796356).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEDD4 | NM_006154.4 | c.1262G>T | p.Gly421Val | missense_variant | 14/29 | ENST00000435532.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEDD4 | ENST00000435532.8 | c.1262G>T | p.Gly421Val | missense_variant | 14/29 | 1 | NM_006154.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251430Hom.: 0 AF XY: 0.0000368 AC XY: 5AN XY: 135882
GnomAD3 exomes
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135882
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461860Hom.: 1 Cov.: 31 AF XY: 0.0000316 AC XY: 23AN XY: 727228
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727228
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
Bravo
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ExAC
?
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5
Asia WGS
AF:
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1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2022 | The c.2303G>T (p.G768V) alteration is located in exon 7 (coding exon 7) of the NEDD4 gene. This alteration results from a G to T substitution at nucleotide position 2303, causing the glycine (G) at amino acid position 768 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;T;D
Polyphen
P;P;B;P
Vest4
MutPred
0.42
.;Loss of disorder (P = 0.0786);.;.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at