rs12039801

Variant names:

• chr1-228181911-G-A
• rs12039801
• NM_001010867.4:c.*6398G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001010867.4(IBA57):​c.*6398G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 152,360 control chromosomes in the GnomAD database, including 193 homozygotes. 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: 𝑓 0.047 (193 hom., cov: 32)
  • Exomes 𝑓: 0.077 (0 hom.)
• Consequence: IBA57 NM_001010867.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.107 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IBA57	NM_001010867.4	MANE Select	c.*6398G>A		3_prime_UTR	Exon 3 of 3	NP_001010867.1
	IBA57	NM_001310327.2		c.*6398G>A		3_prime_UTR	Exon 3 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.*6398G>A		3_prime_UTR	Exon 3 of 3	ENSP00000355672.3
	IBA57	ENST00000484749.5	TSL:5	n.9469G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0467 AC: 7112 AN: 152216 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0491

Gnomad ASJ AF: 0.0423

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0408

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0412

Gnomad OTH AF: 0.0435

GnomAD4 exome AF: 0.0769 AC: 2 AN: 26 Hom.: 0 Cov.: 0 AF XY: 0.111 AC XY: 2 AN XY: 18

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.111 AC: 2 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.0466 AC: 7105 AN: 152334 Hom.: 193 Cov.: 32 AF XY: 0.0477 AC XY: 3552 AN XY: 74498

African (AFR) AF: 0.0436 AC: 1813 AN: 41578

American (AMR) AF: 0.0489 AC: 748 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0423 AC: 147 AN: 3472

East Asian (EAS) AF: 0.115 AC: 596 AN: 5178

South Asian (SAS) AF: 0.0406 AC: 196 AN: 4830

European-Finnish (FIN) AF: 0.0637 AC: 677 AN: 10624

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0412 AC: 2802 AN: 68026

Other (OTH) AF: 0.0430 AC: 91 AN: 2114

Alfa AF: 0.0441 Hom.: 32

Bravo AF: 0.0470

Asia WGS AF: 0.0710 AC: 246 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.0
DANN	Benign	0.74
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Mutation Taster		=100/0	polymorphism (auto)

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: rs12039801; hg19: chr1-228369612;