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GeneBe

16-730510-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_022493.3(CIAO3):c.1338G>A(p.Leu446=) 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

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.403
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]
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.59).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 16-730510-C-T is Benign according to our data. Variant chr16-730510-C-T is described in ClinVar as [Benign]. Clinvar id is 790158.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.403 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0519 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CIAO3NM_022493.3 linkuse as main transcriptc.1338G>A p.Leu446= synonymous_variant 11/11 ENST00000251588.7
CIAO3NM_001304799.2 linkuse as main transcriptc.1032G>A p.Leu344= synonymous_variant 12/12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CIAO3ENST00000251588.7 linkuse as main transcriptc.1338G>A p.Leu446= synonymous_variant 11/111 NM_022493.3 P1Q9H6Q4-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2186
AN:
152264
Hom.:
56
Cov.:
34
show subpopulations
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
GnomAD3 exomes
AF:
0.00389
AC:
963
AN:
247704
Hom.:
23
AF XY:
0.00261
AC XY:
352
AN XY:
134680
show subpopulations
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 SAS exome
AF:
0.000163
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
show subpopulations
Gnomad4 AFR exome
AF:
0.0540
Gnomad4 AMR exome
AF:
0.00280
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000432
Gnomad4 OTH exome
AF:
0.00297
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0144
AC:
2195
AN:
152382
Hom.:
59
Cov.:
34
AF XY:
0.0137
AC XY:
1023
AN XY:
74518
show subpopulations
Gnomad4 AFR
AF:
0.0504
Gnomad4 AMR
AF:
0.00483
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000206
Gnomad4 OTH
AF:
0.00568
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

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.59
Cadd
Benign
4.0
Dann
Benign
0.81

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.

Other links and lift over

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