16-1979197-G-T

Variant names:

• chr16-1979197-G-T
• NM_172167.3:c.971C>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_172167.3(NOXO1):​c.971C>A​(p.Pro324His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,310,744 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NOXO1	NM_172167.3	c.971C>A	p.Pro324His	missense_variant	Exon 8 of 8	ENST00000356120.9	NP_751907.1
TBL3	NM_006453.3	c.*512G>T		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	c.971C>A	p.Pro324His	missense_variant	Exon 8 of 8	1	NM_172167.3	ENSP00000348435.4
TBL3	ENST00000568546.6	c.*512G>T		3_prime_UTR_variant	Exon 22 of 22	1	NM_006453.3	ENSP00000454836.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1310744 Hom.: 0 Cov.: 37 AF XY: 0.00000156 AC XY: 1 AN XY: 641510

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.55e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.65	.;.;D;.
Eigen	Benign	0.14
Eigen_PC	Benign	0.010
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Pathogenic	0.36	D
MetaRNN	Uncertain	0.52	D;D;D;D
MetaSVM	Uncertain	-0.072	T
MutationAssessor	Benign	1.5	.;.;L;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.0	D;D;D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D;D;D
Sift4G	Pathogenic	0.0	D;D;D;D
Polyphen		1.0	D;D;D;D
Vest4		0.40
MutPred		0.23		.;.;Loss of glycosylation at P329 (P = 0.0241);.;
MVP		0.86
MPC		1.0
ClinPred		0.93	D
GERP RS		4.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.9
Varity_R		0.51
gMVP		0.62

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-2029198;