Variant 1-228166080-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001010867.4(IBA57):c.264C>G(p.Ala88Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00517 in 1,537,372 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A88A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.011 ( 44 hom., cov: 34)

Exomes 𝑓: 0.0046 ( 139 hom. )

Consequence

IBA57
NM_001010867.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.51

Variant links:

Genes affected

IBA57 (HGNC:27302): (iron-sulfur cluster assembly factor IBA57) The protein encoded by this gene localizes to the mitochondrion and is part of the iron-sulfur cluster assembly pathway. The encoded protein functions late in the biosynthesis of mitochondrial 4Fe-4S proteins. Defects in this gene have been associated with autosomal recessive spastic paraplegia-74 and with multiple mitochondrial dysfunctions syndrome-3. Two transcript variants encoding different isoforms have been found for this gene. The smaller isoform is not likely to be localized to the mitochondrion since it lacks the amino-terminal transit peptide. [provided by RefSeq, Jul 2015]

IBA57 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-228166080-C-G is Benign according to our data. Variant chr1-228166080-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 382792.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.51 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0781 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IBA57	NM_001010867.4 linkuse as main transcript	c.264C>G	p.Ala88Ala	synonymous_variant	1/3	ENST00000366711.4	NP_001010867.1	Q5T440

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IBA57	ENST00000366711.4 linkuse as main transcript	c.264C>G	p.Ala88Ala	synonymous_variant	1/3	2	NM_001010867.4	ENSP00000355672.3		Q5T440

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1635

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0222

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.0846

Gnomad SAS

AF:

0.0172

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00100

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.0110

AC:

1404

AN:

128192

Hom.:

AF XY:

0.0107

AC XY:

756

AN XY:

70356

show subpopulations

Gnomad AFR exome

AF:

0.0220

Gnomad AMR exome

AF:

0.00154

Gnomad ASJ exome

AF:

0.00475

Gnomad EAS exome

AF:

0.0863

Gnomad SAS exome

AF:

0.0127

Gnomad FIN exome

AF:

0.00483

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00682

GnomAD4 exome

AF:

0.00456

AC:

6319

AN:

1385130

Hom.:

139

Cov.:

AF XY:

0.00473

AC XY:

3236

AN XY:

683638

show subpopulations

Gnomad4 AFR exome

AF:

0.0235

Gnomad4 AMR exome

AF:

0.00182

Gnomad4 ASJ exome

AF:

0.00363

Gnomad4 EAS exome

AF:

0.0785

Gnomad4 SAS exome

AF:

0.0127

Gnomad4 FIN exome

AF:

0.00424

Gnomad4 NFE exome

AF:

0.000972

Gnomad4 OTH exome

AF:

0.00832

GnomAD4 genome

AF:

0.0107

AC:

1634

AN:

152242

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

814

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.0222

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.0847

Gnomad4 SAS

AF:

0.0170

Gnomad4 FIN

AF:

0.00405

Gnomad4 NFE

AF:

0.00100

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.0330

AC:

115

AN:

3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 15, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.5

DANN

Benign

0.59

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