15-55833032-T-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_006154.4(NEDD4):āc.2503A>Gā(p.Met835Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000744 in 1,612,610 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000079 ( 0 hom., cov: 32)
Exomes š: 0.000074 ( 0 hom. )
Consequence
NEDD4
NM_006154.4 missense
NM_006154.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 5.08
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 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NEDD4 | NM_006154.4 | c.2503A>G | p.Met835Val | missense_variant | 27/29 | ENST00000435532.8 | NP_006145.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NEDD4 | ENST00000435532.8 | c.2503A>G | p.Met835Val | missense_variant | 27/29 | 1 | NM_006154.4 | ENSP00000410613.3 |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152164Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250972Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135664
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GnomAD4 exome AF: 0.0000739 AC: 108AN: 1460446Hom.: 0 Cov.: 29 AF XY: 0.0000826 AC XY: 60AN XY: 726622
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GnomAD4 genome AF: 0.0000789 AC: 12AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74320
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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 | Oct 16, 2024 | The c.3544A>G (p.M1182V) alteration is located in exon 20 (coding exon 20) of the NEDD4 gene. This alteration results from a A to G substitution at nucleotide position 3544, causing the methionine (M) at amino acid position 1182 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
Benign
DEOGEN2
Benign
.;T;.;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;.
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Benign
Sift
Benign
T;T;T;T
Sift4G
Benign
T;T;T;T
Polyphen
P;P;P;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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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