16-1979531-A-G

Variant names:

• chr16-1979531-A-G
• rs749378489
• NM_172167.3:c.712T>C

Variant summary

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

The NM_172167.3(NOXO1):​c.712T>C​(p.Cys238Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: NOXO1 NM_172167.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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.712T>C	p.Cys238Arg	missense_variant	Exon 7 of 8	ENST00000356120.9	NP_751907.1
TBL3	NM_006453.3	c.*846A>G		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.712T>C	p.Cys238Arg	missense_variant	Exon 7 of 8	1	NM_172167.3	ENSP00000348435.4
TBL3	ENST00000568546.6	c.*846A>G		3_prime_UTR_variant	Exon 22 of 22	1	NM_006453.3	ENSP00000454836.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 34

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.37	.;.;T;.
Eigen	Benign	0.13
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.66	T;T;T;T
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.51	D;D;D;D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.36	.;.;N;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Pathogenic	-6.0	D;D;D;D
REVEL	Benign	0.25
Sift	Benign	0.035	D;D;D;D
Sift4G	Uncertain	0.042	D;D;D;D
Polyphen		1.0	D;D;D;P
Vest4		0.60
MutPred		0.51		.;.;Gain of MoRF binding (P = 0.0244);.;
MVP		0.26
MPC		1.1
ClinPred		0.62	D
GERP RS		5.1
Varity_R		0.76
gMVP		0.76

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

LitVar

Other links and lift over

dbSNP: rs749378489; hg19: chr16-2029532;