rs368114681

Variant names:

• chr1-228174939-C-A
• rs368114681
• NM_001010867.4:c.589C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-228174939-C-A
• chr1-228174939-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001010867.4(IBA57):​c.589C>A​(p.Arg197Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,424,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: IBA57 NM_001010867.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet
• hereditary spastic paraplegia 74

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

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP7: Synonymous conserved (PhyloP=1.23 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBA57	NM_001010867.4	MANE Select	c.589C>A	p.Arg197Arg	synonymous	Exon 2 of 3	NP_001010867.1
	IBA57	NM_001310327.2		c.10C>A	p.Arg4Arg	synonymous	Exon 2 of 3	NP_001297256.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBA57	ENST00000366711.4	TSL:2 MANE Select	c.589C>A	p.Arg197Arg	synonymous	Exon 2 of 3	ENSP00000355672.3
	IBA57	ENST00000484749.5	TSL:5	n.2589C>A		non_coding_transcript_exon	Exon 2 of 3
	IBA57	ENST00000546123.2	TSL:2	n.309C>A		non_coding_transcript_exon	Exon 2 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.02e-7 AC: 1 AN: 1424804 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 703932

African (AFR) AF: 0.00 AC: 0 AN: 32828

American (AMR) AF: 0.00 AC: 0 AN: 42390

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24294

East Asian (EAS) AF: 0.00 AC: 0 AN: 39140

South Asian (SAS) AF: 0.00 AC: 0 AN: 82978

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48312

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5500

European-Non Finnish (NFE) AF: 9.17e-7 AC: 1 AN: 1090680

Other (OTH) AF: 0.00 AC: 0 AN: 58682

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	13
DANN	Benign	0.85
PhyloP100		1.2
Mutation Taster		=98/2	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

Other links and lift over

dbSNP: rs368114681; hg19: chr1-228362640;