1-183563229-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000433.4(NCF2):ā€‹c.1256A>Gā€‹(p.Asn419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N419I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

NCF2
NM_000433.4 missense

Scores

4
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.63
Variant links:
Genes affected
NCF2 (HGNC:7661): (neutrophil cytosolic factor 2) This gene encodes neutrophil cytosolic factor 2, the 67-kilodalton cytosolic subunit of the multi-protein NADPH oxidase complex found in neutrophils. This oxidase produces a burst of superoxide which is delivered to the lumen of the neutrophil phagosome. Mutations in this gene, as well as in other NADPH oxidase subunits, can result in chronic granulomatous disease, a disease that causes recurrent infections by catalase-positive organisms. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2010]
SMG7 (HGNC:16792): (SMG7 nonsense mediated mRNA decay factor) This gene encodes a protein that is essential for nonsense-mediated mRNA decay (NMD); a process whereby transcripts with premature termination codons are targeted for rapid degradation by a mRNA decay complex. The mRNA decay complex consists, in part, of this protein along with proteins SMG5 and UPF1. The N-terminal domain of this protein is thought to mediate its association with SMG5 or UPF1 while the C-terminal domain interacts with the mRNA decay complex. This protein may therefore couple changes in UPF1 phosphorylation state to the degradation of NMD-candidate transcripts. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Aug 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25976652).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NCF2NM_000433.4 linkc.1256A>G p.Asn419Ser missense_variant Exon 13 of 15 ENST00000367535.8 NP_000424.2 P19878-1A0A0S2Z457

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NCF2ENST00000367535.8 linkc.1256A>G p.Asn419Ser missense_variant Exon 13 of 15 1 NM_000433.4 ENSP00000356505.4 P19878-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461882
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.048
.;.;T;T
Eigen
Benign
0.16
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.79
D
LIST_S2
Uncertain
0.92
D;D;.;D
M_CAP
Benign
0.0097
T
MetaRNN
Benign
0.26
T;T;T;T
MetaSVM
Benign
-0.97
T
MutationAssessor
Uncertain
2.7
.;.;M;M
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.5
N;N;N;N
REVEL
Benign
0.12
Sift
Benign
0.11
T;T;T;T
Sift4G
Benign
0.070
T;T;T;T
Polyphen
0.24
.;.;B;B
Vest4
0.25
MutPred
0.44
.;.;Loss of methylation at K418 (P = 0.1124);Loss of methylation at K418 (P = 0.1124);
MVP
0.56
MPC
0.35
ClinPred
0.64
D
GERP RS
4.5
Varity_R
0.25
gMVP
0.26

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs35012521; hg19: chr1-183532364; API