chr16-730510-C-T

Variant names:

• chr16-730510-C-T
• rs34851515
• NM_022493.3:c.1338G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_022493.3(CIAO3):​c.1338G>A​(p.Leu446Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00272 in 1,610,492 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (59 hom., cov: 34)
  • Exomes 𝑓: 0.0015 (45 hom.)
• Consequence: CIAO3 NM_022493.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.403
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 16-730510-C-T is Benign according to our data. Variant chr16-730510-C-T is described in ClinVar as Benign. ClinVar VariationId is 790158.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.403 with no splicing effect.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIAO3	NM_022493.3	MANE Select	c.1338G>A	p.Leu446Leu	synonymous	Exon 11 of 11	NP_071938.1	Q9H6Q4-1
	CIAO3	NM_001304799.2		c.1032G>A	p.Leu344Leu	synonymous	Exon 12 of 12	NP_001291728.1	Q9H6Q4-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CIAO3	ENST00000251588.7	TSL:1 MANE Select	c.1338G>A	p.Leu446Leu	synonymous	Exon 11 of 11	ENSP00000251588.2	Q9H6Q4-1
	CIAO3	ENST00000562862.5	TSL:1	n.1254G>A		non_coding_transcript_exon	Exon 6 of 6
	CIAO3	ENST00000946067.1		c.1362G>A	p.Leu454Leu	synonymous	Exon 12 of 12	ENSP00000616126.1

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2186 AN: 152264 Hom.: 56 Cov.: 34

Gnomad AFR AF: 0.0503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00484

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00389 AC: 963 AN: 247704 AF XY: 0.00261

Gnomad AFR exome AF: 0.0521

Gnomad AMR exome AF: 0.00289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.000985

GnomAD4 exome AF: 0.00150 AC: 2189 AN: 1458110 Hom.: 45 Cov.: 32 AF XY: 0.00124 AC XY: 896 AN XY: 725502

African (AFR) AF: 0.0540 AC: 1808 AN: 33478

American (AMR) AF: 0.00280 AC: 125 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000151 AC: 13 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49730

Middle Eastern (MID) AF: 0.00277 AC: 16 AN: 5768

European-Non Finnish (NFE) AF: 0.0000432 AC: 48 AN: 1111960

Other (OTH) AF: 0.00297 AC: 179 AN: 60362

GnomAD4 genome AF: 0.0144 AC: 2195 AN: 152382 Hom.: 59 Cov.: 34 AF XY: 0.0137 AC XY: 1023 AN XY: 74518

African (AFR) AF: 0.0504 AC: 2094 AN: 41588

American (AMR) AF: 0.00483 AC: 74 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 68036

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00684 Hom.: 8

Bravo AF: 0.0170

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.0
DANN	Benign	0.81
PhyloP100		0.40
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34851515; hg19: chr16-780510; COSMIC: COSV52400509; COSMIC: COSV52400509;