chr11-89421913-C-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016931.5(NOX4):c.618G>T(p.Leu206Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000211 in 1,565,526 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
NOX4
NM_016931.5 missense
NM_016931.5 missense
Scores
11
6
Clinical Significance
Conservation
PhyloP100: 0.0130
Genes affected
NOX4 (HGNC:7891): (NADPH oxidase 4) This gene encodes a member of the NOX-family of enzymes that functions as the catalytic subunit the NADPH oxidase complex. The encoded protein is localized to non-phagocytic cells where it acts as an oxygen sensor and catalyzes the reduction of molecular oxygen to various reactive oxygen species (ROS). The ROS generated by this protein have been implicated in numerous biological functions including signal transduction, cell differentiation and tumor cell growth. A pseudogene has been identified on the other arm of chromosome 11. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Jan 2009]
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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 | UniProt |
---|---|---|---|---|---|---|---|
NOX4 | NM_016931.5 | c.618G>T | p.Leu206Phe | missense_variant | 8/18 | ENST00000263317.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NOX4 | ENST00000263317.9 | c.618G>T | p.Leu206Phe | missense_variant | 8/18 | 1 | NM_016931.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152046Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000473 AC: 1AN: 211336Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 115066
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GnomAD4 exome AF: 0.0000212 AC: 30AN: 1413362Hom.: 0 Cov.: 27 AF XY: 0.0000213 AC XY: 15AN XY: 702958
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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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 | Feb 14, 2023 | The c.618G>T (p.L206F) alteration is located in exon 8 (coding exon 8) of the NOX4 gene. This alteration results from a G to T substitution at nucleotide position 618, causing the leucine (L) at amino acid position 206 to be replaced by a phenylalanine (F). 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
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D;.;D;T;D;D;.;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
N;N;N;N;N;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;D;T;T;T;T;D;T;T
Sift4G
Benign
T;T;T;D;T;T;T;T;T
Polyphen
0.35, 0.0030, 0.28, 0.042, 0.87
.;.;B;B;B;.;.;B;P
Vest4
MutPred
0.78
.;.;Loss of stability (P = 0.0855);Loss of stability (P = 0.0855);Loss of stability (P = 0.0855);.;.;.;.;
MVP
MPC
0.055
ClinPred
T
GERP RS
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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