rs201565784

Variant names:

• chr16-1979521-C-T
• rs201565784
• NM_172167.3:c.722G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_172167.3(NOXO1):​c.722G>A​(p.Arg241His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,611,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 34)
  • Exomes 𝑓: 0.00028 (1 hom.)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.12
• Publications: 5 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.

• BP4: Computational evidence support a benign effect (MetaRNN=0.069181114).

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.722G>A	p.Arg241His	missense	Exon 7 of 8	NP_751907.1	Q8NFA2-3
	TBL3	NM_006453.3	MANE Select	c.*836C>T		3_prime_UTR	Exon 22 of 22	NP_006444.2
	NOXO1	NM_172168.3		c.737G>A	p.Arg246His	missense	Exon 7 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.722G>A	p.Arg241His	missense	Exon 7 of 8	ENSP00000348435.4	Q8NFA2-3
	NOXO1	ENST00000397280.8	TSL:1	c.737G>A	p.Arg246His	missense	Exon 7 of 8	ENSP00000380450.4	Q8NFA2-1
	NOXO1	ENST00000566005.5	TSL:1	c.734G>A	p.Arg245His	missense	Exon 7 of 8	ENSP00000456800.1	Q8NFA2-2

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152232 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000544

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000278 AC: 68 AN: 244958 AF XY: 0.000255

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000584

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000333

Gnomad FIN exome AF: 0.000812

Gnomad NFE exome AF: 0.000382

Gnomad OTH exome AF: 0.000167

GnomAD4 exome AF: 0.000280 AC: 408 AN: 1458890 Hom.: 1 Cov.: 34 AF XY: 0.000274 AC XY: 199 AN XY: 725620

African (AFR) AF: 0.0000299 AC: 1 AN: 33430

American (AMR) AF: 0.0000673 AC: 3 AN: 44546

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26022

East Asian (EAS) AF: 0.000378 AC: 15 AN: 39656

South Asian (SAS) AF: 0.00 AC: 0 AN: 86060

European-Finnish (FIN) AF: 0.000632 AC: 33 AN: 52184

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.000311 AC: 345 AN: 1110972

Other (OTH) AF: 0.000166 AC: 10 AN: 60262

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152350 Hom.: 0 Cov.: 34 AF XY: 0.000228 AC XY: 17 AN XY: 74508

African (AFR) AF: 0.0000241 AC: 1 AN: 41576

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000544 AC: 37 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000459 Hom.: 0

Bravo AF: 0.000200

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000590 AC: 5

ExAC AF: 0.000240 AC: 29

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.069	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N
PhyloP100		-1.1
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.074
Sift	Uncertain	0.029	D
Sift4G	Benign	0.066	T
Polyphen		0.99	D
Vest4		0.15
MVP		0.24
MPC		0.35
ClinPred		0.12	T
GERP RS		-5.7
Varity_R		0.078
gMVP		0.51
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs201565784; hg19: chr16-2029522;