rs61743941

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001010867.4(IBA57):c.645C>A(p.Asp215Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,397,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D215D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

IBA57
NM_001010867.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0850

Publications

0 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, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hereditary spastic paraplegia 74
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

IBA57 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11965212).

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.645C>A	p.Asp215Glu	missense	Exon 2 of 3	NP_001010867.1	Q5T440
	IBA57	NM_001310327.2		c.66C>A	p.Asp22Glu	missense	Exon 2 of 3	NP_001297256.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IBA57	ENST00000366711.4	TSL:2 MANE Select	c.645C>A	p.Asp215Glu	missense	Exon 2 of 3	ENSP00000355672.3	Q5T440
IBA57	ENST00000949083.1		c.639C>A	p.Asp213Glu	missense	Exon 2 of 3	ENSP00000619142.1
IBA57	ENST00000484749.5	TSL:5	n.2645C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.16e-7

AC:

AN:

1397202

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

686610

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32002

American (AMR)

AF:

0.00

AC:

AN:

38880

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22002

East Asian (EAS)

AF:

0.00

AC:

AN:

39006

South Asian (SAS)

AF:

0.0000130

AC:

AN:

76772

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5446

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1076908

Other (OTH)

AF:

0.00

AC:

AN:

57468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.0

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0082

Eigen

Benign

-0.88

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.56

M_CAP

Benign

0.035

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.75

MutationAssessor

Uncertain

2.1

PhyloP100

-0.085

PrimateAI

Benign

0.35

PROVEAN

Benign

-1.9

REVEL

Benign

0.059

Sift

Benign

0.030

Sift4G

Benign

0.064

Polyphen

0.15

Vest4

0.14

MutPred

0.58

Gain of catalytic residue at W217 (P = 0.0604)

MVP

0.45

MPC

0.25

ClinPred

0.16

GERP RS

0.77

Varity_R

0.17

gMVP

0.64

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over