Variant 16-730575-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.1273G>A(p.Gly425Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0016 in 1,611,034 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 34)

Exomes 𝑓: 0.0016 ( 6 hom. )

Consequence

CIAO3
NM_022493.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.40

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=0.004664868).

BP6

Variant 16-730575-C-T is Benign according to our data. Variant chr16-730575-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 718886.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CIAO3	NM_022493.3 linkuse as main transcript	c.1273G>A	p.Gly425Ser	missense_variant	11/11	ENST00000251588.7	NP_071938.1
CIAO3	NM_001304799.2 linkuse as main transcript	c.967G>A	p.Gly323Ser	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.1273G>A	p.Gly425Ser	missense_variant	11/11	1	NM_022493.3	ENSP00000251588	P1	Q9H6Q4-1

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00179

AC:

443

AN:

247108

Hom.:

AF XY:

0.00178

AC XY:

240

AN XY:

134578

show subpopulations

Gnomad AFR exome

AF:

0.000251

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00213

Gnomad SAS exome

AF:

0.00219

Gnomad FIN exome

AF:

0.00300

Gnomad NFE exome

AF:

0.00235

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00161

AC:

2355

AN:

1458650

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

1188

AN XY:

725708

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00164

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.00262

Gnomad4 NFE exome

AF:

0.00162

Gnomad4 OTH exome

AF:

0.00229

GnomAD4 genome

AF:

0.00142

AC:

216

AN:

152384

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

104

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00106

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00175

AC:

ExAC

AF:

0.00191

AC:

232

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00113

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

Dec 04, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0070

DANN

Benign

0.87

DEOGEN2

Benign

0.048

T;.;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.34

T;.;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.0047

T;T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

1.0

N;N;N

REVEL

Benign

0.010

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.73

T;T;T

Polyphen

0.0010

B;.;.

Vest4

0.050

MVP

0.14

MPC

0.16

ClinPred

0.0027

GERP RS

-3.7

Varity_R

0.039

gMVP

0.32

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