rs1189542525

Variant names:

• chr1-228165808-T-A
• rs1189542525
• NM_001010867.4:c.-9T>A

Your query was ambiguous. Multiple possible variants found:

• chr1-228165808-T-A
• chr1-228165808-T-C
• chr1-228165808-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001010867.4(IBA57):​c.-9T>A variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000876 in 1,141,490 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: 32)
  • Exomes 𝑓: 8.8e-7 (0 hom.)
• Consequence: IBA57 NM_001010867.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• 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-DT (HGNC:32062): (IBA57 divergent transcript)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-9T>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001010867.1	Q5T440
	IBA57	NM_001010867.4	MANE Select	c.-9T>A		5_prime_UTR	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.-9T>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000355672.3	Q5T440
	IBA57	ENST00000366711.4	TSL:2 MANE Select	c.-9T>A		5_prime_UTR	Exon 1 of 3	ENSP00000355672.3	Q5T440
	IBA57	ENST00000949083.1		c.-9T>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000619142.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.76e-7 AC: 1 AN: 1141490 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 547526

African (AFR) AF: 0.00 AC: 0 AN: 23238

American (AMR) AF: 0.00 AC: 0 AN: 10230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15020

East Asian (EAS) AF: 0.00 AC: 0 AN: 26954

South Asian (SAS) AF: 0.00 AC: 0 AN: 34962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25180

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3066

European-Non Finnish (NFE) AF: 0.00000105 AC: 1 AN: 956602

Other (OTH) AF: 0.00 AC: 0 AN: 46238

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		-0.53
PromoterAI		-0.018	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1189542525; hg19: chr1-228353509;