Genetic Variant NOXO1:p.Asp305His (chr16-1979255-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_172167.3(NOXO1):c.913G>C(p.Asp305His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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. D305N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NOXO1
NM_172167.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.672

Publications

0 publications found

Variant links:

Genes affected

NOXO1 (HGNC:19404): (NADPH oxidase organizer 1) This gene encodes an NADPH oxidase (NOX) organizer, which positively regulates NOX1 and NOX3. The protein contains a PX domain and two SH3 domains. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2012]

NOXO1 links:

TBL3 (HGNC:11587): (transducin beta like 3) The protein encoded by this gene has sequence similarity with members of the WD40 repeat-containing protein family. The WD40 group is a large family of proteins, which appear to have a regulatory function. It is believed that the WD40 repeats mediate protein-protein interactions and members of the family are involved in signal transduction, RNA processing, gene regulation, vesicular trafficking, cytoskeletal assembly and may play a role in the control of cytotypic differentiation. This gene has multiple polyadenylation sites. It might have multiple alternatively spliced transcript variants but the variants have not been fully described yet. [provided by RefSeq, Jul 2008]

TBL3 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07822263).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_172167.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXO1	NM_172167.3	MANE Select	c.913G>C	p.Asp305His	missense	Exon 8 of 8	NP_751907.1	Q8NFA2-3
TBL3	NM_006453.3	MANE Select	c.*570C>G		3_prime_UTR	Exon 22 of 22	NP_006444.2
NOXO1	NM_172168.3		c.928G>C	p.Asp310His	missense	Exon 8 of 8	NP_751908.1	Q8NFA2-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NOXO1	ENST00000356120.9	TSL:1 MANE Select	c.913G>C	p.Asp305His	missense	Exon 8 of 8	ENSP00000348435.4	Q8NFA2-3
NOXO1	ENST00000397280.8	TSL:1	c.928G>C	p.Asp310His	missense	Exon 8 of 8	ENSP00000380450.4	Q8NFA2-1
NOXO1	ENST00000566005.5	TSL:1	c.925G>C	p.Asp309His	missense	Exon 8 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1372220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

677224

African (AFR)

AF:

0.00

AC:

AN:

29788

American (AMR)

AF:

0.00

AC:

AN:

33878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24296

East Asian (EAS)

AF:

0.00

AC:

AN:

34770

South Asian (SAS)

AF:

0.00

AC:

AN:

78044

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35048

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4418

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074850

Other (OTH)

AF:

0.00

AC:

AN:

57128

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000950

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.061

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.51

M_CAP

Benign

0.023

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.69

PhyloP100

-0.67

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.59

REVEL

Benign

0.088

Sift

Uncertain

0.028

Sift4G

Benign

0.16

Polyphen

0.47

Vest4

0.066

MutPred

0.23

Gain of catalytic residue at D309 (P = 0.1181)

MVP

0.47

MPC

0.33

ClinPred

0.12

GERP RS

-5.8

Varity_R

0.062

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over