rs35651739

chr16-1980097-G-A

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP7 BS2

The NM_172167.3(NOXO1):c.486C>T(p.Ser162=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.640

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

Verdict is Benign. Variant got -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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NOXO1	NM_172167.3	c.486C>T	p.Ser162=	synonymous_variant	5/8	ENST00000356120.9
TBL3	NM_006453.3	c.*1412G>A		3_prime_UTR_variant	22/22	ENST00000568546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NOXO1	ENST00000356120.9	c.486C>T	p.Ser162=	synonymous_variant	5/8	1	NM_172167.3	P2
TBL3	ENST00000568546.6	c.*1412G>A		3_prime_UTR_variant	22/22	1	NM_006453.3	P1

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 393 AN: 152242 Hom.: 2 Cov.: 33

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

GnomAD3 exomes AF: 0.000659 AC: 156 AN: 236648 Hom.: 0 AF XY: 0.000457 AC XY: 59 AN XY: 129110

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 SAS exome AF: 0.0000340

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.: 1 Cov.: 33 AF XY: 0.000265 AC XY: 192 AN XY: 723508

Gnomad4 AFR exome AF: 0.00915

Gnomad4 AMR exome AF: 0.000545

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000469

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000324

Gnomad4 OTH exome AF: 0.000616

GnomAD4 genome AF: 0.00266 AC: 405 AN: 152360 Hom.: 4 Cov.: 33 AF XY: 0.00275 AC XY: 205 AN XY: 74510

Gnomad4 AFR AF: 0.00945

Gnomad4 AMR AF: 0.000392

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.00304

Asia WGS AF: 0.000866 AC: 3 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
Dann	Benign	0.92
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

LitVar

Other links and lift over

dbSNP: rs35651739; hg19: chr16-2030098;