rs761905522

Variant names:

• chr16-1979291-C-G
• rs761905522
• NM_172167.3:c.877G>C

Your query was ambiguous. Multiple possible variants found:

• chr16-1979291-C-G
• chr16-1979291-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_172167.3(NOXO1):​c.877G>C​(p.Ala293Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000071 in 1,408,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. A293T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0640
• 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: 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=0.16342866).

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.877G>C	p.Ala293Pro	missense	Exon 8 of 8	NP_751907.1	Q8NFA2-3
	TBL3	NM_006453.3	MANE Select	c.*606C>G		3_prime_UTR	Exon 22 of 22	NP_006444.2
	NOXO1	NM_172168.3		c.892G>C	p.Ala298Pro	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.877G>C	p.Ala293Pro	missense	Exon 8 of 8	ENSP00000348435.4	Q8NFA2-3
	NOXO1	ENST00000397280.8	TSL:1	c.892G>C	p.Ala298Pro	missense	Exon 8 of 8	ENSP00000380450.4	Q8NFA2-1
	NOXO1	ENST00000566005.5	TSL:1	c.889G>C	p.Ala297Pro	missense	Exon 8 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1408428 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 698036

African (AFR) AF: 0.00 AC: 0 AN: 31890

American (AMR) AF: 0.00 AC: 0 AN: 40026

Ashkenazi Jewish (ASJ) AF: 0.0000397 AC: 1 AN: 25220

East Asian (EAS) AF: 0.00 AC: 0 AN: 36840

South Asian (SAS) AF: 0.00 AC: 0 AN: 81466

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36442

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5070

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092916

Other (OTH) AF: 0.00 AC: 0 AN: 58558

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.3
DANN	Benign	0.96
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.69	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.87	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.064
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.13
Sift	Benign	0.089	T
Sift4G	Benign	0.16	T
Polyphen		0.98	D
Vest4		0.079
MutPred		0.26		Gain of disorder (P = 0.0418)
MVP		0.48
MPC		0.75
ClinPred		0.30	T
GERP RS		-3.9
Varity_R		0.11
gMVP		0.46

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

Other links and lift over

dbSNP: rs761905522; hg19: chr16-2029292;