rs13375853

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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:4

Conservation

PhyloP100: -2.51

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
multiple mitochondrial dysfunctions syndrome 3
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
hereditary spastic paraplegia 74
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

IBA57 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001010867.4. 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
	IBA57	NM_001010867.4	MANE Select	c.264C>G	p.Ala88Ala	synonymous	Exon 1 of 3	NP_001010867.1	Q5T440

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBA57	ENST00000366711.4	TSL:2 MANE Select	c.264C>G	p.Ala88Ala	synonymous	Exon 1 of 3	ENSP00000355672.3	Q5T440
	IBA57	ENST00000949083.1		c.264C>G	p.Ala88Ala	synonymous	Exon 1 of 3	ENSP00000619142.1

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

GnomAD2 exomes

AF:

0.0110

AC:

1404

AN:

128192

AF XY:

0.0107

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 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

African (AFR)

AF:

0.0235

AC:

707

AN:

30110

American (AMR)

AF:

0.00182

AC:

AN:

35162

Ashkenazi Jewish (ASJ)

AF:

0.00363

AC:

AN:

24826

East Asian (EAS)

AF:

0.0785

AC:

2740

AN:

34914

South Asian (SAS)

AF:

0.0127

AC:

990

AN:

77844

European-Finnish (FIN)

AF:

0.00424

AC:

179

AN:

42246

Middle Eastern (MID)

AF:

0.00389

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.000972

AC:

1047

AN:

1076702

Other (OTH)

AF:

0.00832

AC:

480

AN:

57664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

361

723

1084

1446

1807

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0107

AC:

1634

AN:

152242

Hom.:

Cov.:

AF XY:

0.0109

AC XY:

814

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.0222

AC:

921

AN:

41516

American (AMR)

AF:

0.00320

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3470

East Asian (EAS)

AF:

0.0847

AC:

439

AN:

5184

South Asian (SAS)

AF:

0.0170

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00100

AC:

AN:

68004

Other (OTH)

AF:

0.00804

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

162

242

323

404

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.0113

Asia WGS

AF:

0.0330

AC:

115

AN:

3462

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.5

(source)

DANN

Benign

0.59

PhyloP100

-2.5

PromoterAI

0.0047

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over