16-730558-C-G

Variant names:

• chr16-730558-C-G
• NM_022493.3:c.1290G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_022493.3(CIAO3):​c.1290G>C​(p.Glu430Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CIAO3 NM_022493.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.372

Genes affected

CIAO3 (HGNC:14179): (cytosolic iron-sulfur assembly component 3) Predicted to enable 4 iron, 4 sulfur cluster binding activity. Involved in several processes, including iron-sulfur cluster assembly; oxygen homeostasis; and response to hypoxia. Part of CIA complex. [provided by Alliance of Genome Resources, Apr 2022]

HAGHL (HGNC:14177): (hydroxyacylglutathione hydrolase like) Predicted to enable hydroxyacylglutathione hydrolase activity and metal ion binding activity. Predicted to be involved in methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113112).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CIAO3	NM_022493.3	c.1290G>C	p.Glu430Asp	missense_variant	Exon 11 of 11	ENST00000251588.7	NP_071938.1
CIAO3	NM_001304799.2	c.984G>C	p.Glu328Asp	missense_variant	Exon 12 of 12		NP_001291728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CIAO3	ENST00000251588.7	c.1290G>C	p.Glu430Asp	missense_variant	Exon 11 of 11	1	NM_022493.3	ENSP00000251588.2

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458608 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 725694

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: 8.99e-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	0.12
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	4.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.15	T;.;.
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.50	D
LIST_S2	Benign	0.67	T;.;T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.94	T
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N;N;N
REVEL	Benign	0.063
Sift	Benign	0.45	T;T;T
Sift4G	Benign	0.39	T;T;T
Polyphen		0.17	B;.;.
Vest4		0.14
MutPred		0.34		Loss of helix (P = 0.0376);.;.;
MVP		0.33
MPC		0.27
ClinPred		0.33	T
GERP RS		-3.0
Varity_R		0.24
gMVP		0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr16-780558;