chr6-11190175-T-C
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_006403.4(NEDD9):c.1694A>G(p.His565Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,614,218 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00017 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00017 ( 3 hom. )
Consequence
NEDD9
NM_006403.4 missense
NM_006403.4 missense
Scores
19
Clinical Significance
Conservation
PhyloP100: -0.00500
Genes affected
NEDD9 (HGNC:7733): (neural precursor cell expressed, developmentally down-regulated 9) The protein encoded by this gene is a member of the CRK-associated substrates family. Members of this family are adhesion docking molecules that mediate protein-protein interactions for signal transduction pathways. This protein is a focal adhesion protein that acts as a scaffold to regulate signaling complexes important in cell attachment, migration and invasion as well as apoptosis and the cell cycle. This protein has also been reported to have a role in cancer metastasis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2012]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0039544106).
BS2
?
High AC in GnomAd at 26 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NEDD9 | NM_006403.4 | c.1694A>G | p.His565Arg | missense_variant | 5/7 | ENST00000379446.10 | |
NEDD9 | NM_001142393.2 | c.1694A>G | p.His565Arg | missense_variant | 6/8 | ||
NEDD9 | NM_001271033.2 | c.1247A>G | p.His416Arg | missense_variant | 4/6 | ||
NEDD9 | NR_073131.1 | n.2301A>G | non_coding_transcript_exon_variant | 8/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NEDD9 | ENST00000379446.10 | c.1694A>G | p.His565Arg | missense_variant | 5/7 | 1 | NM_006403.4 | P4 | |
ENST00000500636.2 | n.175+4957T>C | intron_variant, non_coding_transcript_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 26AN: 152214Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000319 AC: 80AN: 251140Hom.: 1 AF XY: 0.000324 AC XY: 44AN XY: 135716
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GnomAD4 exome AF: 0.000170 AC: 249AN: 1461886Hom.: 3 Cov.: 30 AF XY: 0.000179 AC XY: 130AN XY: 727244
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GnomAD4 genome ? AF: 0.000171 AC: 26AN: 152332Hom.: 0 Cov.: 32 AF XY: 0.000134 AC XY: 10AN XY: 74498
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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 | Jul 14, 2021 | The c.1694A>G (p.H565R) alteration is located in exon 6 (coding exon 5) of the NEDD9 gene. This alteration results from a A to G substitution at nucleotide position 1694, causing the histidine (H) at amino acid position 565 to be replaced by an arginine (R). 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
Benign
Dann
Benign
DEOGEN2
Benign
T;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;N
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N
REVEL
Benign
Sift
Benign
T;.;T
Sift4G
Benign
T;T;T
Polyphen
B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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