NM_172167.3:c.1024G>C

Variant names:

• chr16-1979144-C-G
• rs757511336
• NM_172167.3:c.1024G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_172167.3(NOXO1):​c.1024G>C​(p.Val342Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,314,972 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. V342I) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.51
• Publications: 0 publications found

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]

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0534575).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXO1	NM_172167.3	MANE Select	c.1024G>C	p.Val342Leu	missense	Exon 8 of 8	NP_751907.1	Q8NFA2-3
	TBL3	NM_006453.3	MANE Select	c.*459C>G		3_prime_UTR	Exon 22 of 22	NP_006444.2
	NOXO1	NM_172168.3		c.1039G>C	p.Val347Leu	missense	Exon 8 of 8	NP_751908.1	Q8NFA2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOXO1	ENST00000356120.9	TSL:1 MANE Select	c.1024G>C	p.Val342Leu	missense	Exon 8 of 8	ENSP00000348435.4	Q8NFA2-3
	NOXO1	ENST00000397280.8	TSL:1	c.1039G>C	p.Val347Leu	missense	Exon 8 of 8	ENSP00000380450.4	Q8NFA2-1
	NOXO1	ENST00000566005.5	TSL:1	c.1036G>C	p.Val346Leu	missense	Exon 8 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000152 AC: 2 AN: 1314972 Hom.: 0 Cov.: 34 AF XY: 0.00000155 AC XY: 1 AN XY: 645830

African (AFR) AF: 0.00 AC: 0 AN: 25858

American (AMR) AF: 0.00 AC: 0 AN: 20076

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21948

East Asian (EAS) AF: 0.00 AC: 0 AN: 32136

South Asian (SAS) AF: 0.00 AC: 0 AN: 71156

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32524

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3852

European-Non Finnish (NFE) AF: 0.00000190 AC: 2 AN: 1052842

Other (OTH) AF: 0.00 AC: 0 AN: 54580

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	13
DANN	Benign	0.88
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-2.5
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.073
Sift	Benign	0.042	D
Sift4G	Benign	0.17	T
Polyphen		0.0010	B
Vest4		0.040
MutPred		0.26		Loss of catalytic residue at V347 (P = 0.0398)
MVP		0.29
MPC		0.27
ClinPred		0.070	T
GERP RS		-3.4
Varity_R		0.085
gMVP		0.20
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs757511336; hg19: chr16-2029145;