1-228166131-G-A

Variant names:

• chr1-228166131-G-A
• rs2034849093
• NM_001010867.4:c.315G>A
• IBA57 p.Arg105Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001010867.4(IBA57):​c.315G>A​(p.Arg105Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IBA57 NM_001010867.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00400
• Publications: 0 publications found

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: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 74

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BP6: Variant 1-228166131-G-A is Benign according to our data. Variant chr1-228166131-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2933787.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.004 with no splicing effect.

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.315G>A	p.Arg105Arg	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.315G>A	p.Arg105Arg	synonymous	Exon 1 of 3	ENSP00000355672.3	Q5T440
	IBA57	ENST00000949083.1		c.315G>A	p.Arg105Arg	synonymous	Exon 1 of 3	ENSP00000619142.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369726 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 675864

African (AFR) AF: 0.00 AC: 0 AN: 28938

American (AMR) AF: 0.00 AC: 0 AN: 31682

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23852

East Asian (EAS) AF: 0.00 AC: 0 AN: 33764

South Asian (SAS) AF: 0.00 AC: 0 AN: 76430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44470

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1068296

Other (OTH) AF: 0.00 AC: 0 AN: 56734

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Multiple mitochondrial dysfunctions syndrome 3;C5568837:Hereditary spastic paraplegia 74 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	12
DANN	Benign	0.96
PhyloP100		0.0040
PromoterAI		-0.015	Neutral
Mutation Taster		=99/1	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2034849093;

hg19: chr1-228353832;