Genetic Variant NM_172167.3:c.486C>T (chr16-1980097-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_172167.3(NOXO1):c.486C>T(p.Ser162Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00051 in 1,607,758 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00029 ( 1 hom. )

Consequence

NOXO1
NM_172167.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.640

Publications

2 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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP7

Synonymous conserved (PhyloP=0.64 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOXO1	NM_172167.3 link	c.486C>T	p.Ser162Ser	synonymous_variant	Exon 5 of 8	ENST00000356120.9	NP_751907.1
TBL3	NM_006453.3 link	c.*1412G>A		3_prime_UTR_variant	Exon 22 of 22	ENST00000568546.6	NP_006444.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NOXO1	ENST00000356120.9 link	c.486C>T	p.Ser162Ser	synonymous_variant	Exon 5 of 8	1	NM_172167.3	ENSP00000348435.4
TBL3	ENST00000568546.6 link	c.*1412G>A		3_prime_UTR_variant	Exon 22 of 22	1	NM_006453.3	ENSP00000454836.1

Frequencies

GnomAD3 genomes

AF:

0.00258

AC:

393

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00919

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.000659

AC:

156

AN:

236648

AF XY:

0.000457

show subpopulations

Gnomad AFR exome

AF:

0.00875

Gnomad AMR exome

AF:

0.000629

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000375

Gnomad OTH exome

AF:

0.000346

GnomAD4 exome

AF:

0.000285

AC:

415

AN:

1455398

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

192

AN XY:

723508

show subpopulations

African (AFR)

AF:

0.00915

AC:

306

AN:

33426

American (AMR)

AF:

0.000545

AC:

AN:

44036

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25998

East Asian (EAS)

AF:

0.00

AC:

AN:

39560

South Asian (SAS)

AF:

0.0000469

AC:

AN:

85294

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51532

Middle Eastern (MID)

AF:

0.00167

AC:

AN:

4788

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1110674

Other (OTH)

AF:

0.000616

AC:

AN:

60090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

108

135

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00266

AC:

405

AN:

152360

Hom.:

Cov.:

AF XY:

0.00275

AC XY:

205

AN XY:

74510

show subpopulations

African (AFR)

AF:

0.00945

AC:

393

AN:

41584

American (AMR)

AF:

0.000392

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68028

Other (OTH)

AF:

0.00236

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00276

Hom.:

Bravo

AF:

0.00304

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

CADD

Benign

9.5

(source)

DANN

Benign

0.92

PhyloP100

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over