Variant 16-730545-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_022493.3(CIAO3):c.1303G>A(p.Ala435Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,610,970 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 3 hom., cov: 34)

Exomes 𝑓: 0.00046 ( 2 hom. )

Consequence

CIAO3
NM_022493.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.969

Variant links:

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]

CIAO3 links:

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]

HAGHL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004642874).

BP6

Variant 16-730545-C-T is Benign according to our data. Variant chr16-730545-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 723437.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIAO3	NM_022493.3 linkuse as main transcript	c.1303G>A	p.Ala435Thr	missense_variant	11/11	ENST00000251588.7	NP_071938.1
CIAO3	NM_001304799.2 linkuse as main transcript	c.997G>A	p.Ala333Thr	missense_variant	12/12		NP_001291728.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CIAO3	ENST00000251588.7 linkuse as main transcript	c.1303G>A	p.Ala435Thr	missense_variant	11/11	1	NM_022493.3	ENSP00000251588	P1	Q9H6Q4-1

Frequencies

GnomAD3 genomes

AF:

0.00106

AC:

162

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00280

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00476

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000860

AC:

213

AN:

247652

Hom.:

AF XY:

0.00109

AC XY:

147

AN XY:

134760

show subpopulations

Gnomad AFR exome

AF:

0.00311

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00431

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000223

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000464

AC:

677

AN:

1458582

Hom.:

Cov.:

AF XY:

0.000615

AC XY:

446

AN XY:

725698

show subpopulations

Gnomad4 AFR exome

AF:

0.00284

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00474

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000113

Gnomad4 OTH exome

AF:

0.000480

GnomAD4 genome

AF:

0.00110

AC:

167

AN:

152388

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.00291

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00476

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000588

Hom.:

Bravo

AF:

0.00115

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00295

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000990

AC:

120

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000415

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.63

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.045

T;.;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.34

T;.;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.0046

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

1.0

N;N;N

REVEL

Benign

0.039

Sift

Benign

0.13

T;T;T

Sift4G

Benign

0.22

T;T;T

Polyphen

0.021

B;.;.

Vest4

0.063

MVP

0.31

MPC

0.16

ClinPred

0.0064

GERP RS

2.6

Varity_R

0.063

gMVP

0.31

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over