chr1-228165827-C-G

Variant names:

• chr1-228165827-C-G
• NM_001010867.4:c.11C>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001010867.4(IBA57):​c.11C>G​(p.Ala4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000087 in 1,149,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A4V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.7e-7 (0 hom.)
• Consequence: IBA57 NM_001010867.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.185

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32055426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IBA57	NM_001010867.4	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 3	ENST00000366711.4	NP_001010867.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IBA57	ENST00000366711.4	c.11C>G	p.Ala4Gly	missense_variant	Exon 1 of 3	2	NM_001010867.4	ENSP00000355672.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.70e-7 AC: 1 AN: 1149202 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 552400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000104

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.0027	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.36	T
M_CAP	Pathogenic	0.60	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.73	N
REVEL	Benign	0.055
Sift	Benign	0.052	T
Sift4G	Benign	0.062	T
Polyphen		0.97	D
Vest4		0.29
MutPred		0.20		Loss of helix (P = 0.0167);
MVP		0.44
MPC		0.39
ClinPred		0.37	T
GERP RS		2.8
Varity_R		0.080
gMVP		0.38

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-228353528;