rs1886970

chr13-23866359-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005932.4(MIPEP):c.944-2170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,010 control chromosomes in the GnomAD database, including 11,537 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 0.39 (11537 hom., cov: 32)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160

Genes affected

MIPEP (HGNC:7104): (mitochondrial intermediate peptidase) The product of this gene performs the final step in processing a specific class of nuclear-encoded proteins targeted to the mitochondrial matrix or inner membrane. This protein is primarily involved in the maturation of oxidative phosphorylation (OXPHOS)-related proteins. This gene may contribute to the functional effects of frataxin deficiency and the clinical manifestations of Friedreich ataxia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIPEP	NM_005932.4	c.944-2170A>G		intron_variant		ENST00000382172.4
MIPEP	XM_011535097.3	c.758-2170A>G		intron_variant
MIPEP	XM_011535098.4	c.944-2170A>G		intron_variant
MIPEP	XM_047430368.1	c.758-2170A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIPEP	ENST00000382172.4	c.944-2170A>G		intron_variant		1	NM_005932.4	P1
MIPEP	ENST00000494139.1	n.341-2170A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58762 AN: 151892 Hom.: 11536 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.406

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.397

Gnomad OTH AF: 0.377

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.387 AC: 58790 AN: 152010 Hom.: 11537 Cov.: 32 AF XY: 0.385 AC XY: 28608 AN XY: 74318

Gnomad4 AFR AF: 0.385

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.369

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.406

Gnomad4 NFE AF: 0.397

Gnomad4 OTH AF: 0.373

Alfa AF: 0.383 Hom.: 6281

Bravo AF: 0.387

Asia WGS AF: 0.302 AC: 1050 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	3.5
Dann	Benign	0.49

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

LitVar

Other links and lift over

dbSNP: rs1886970; hg19: chr13-24440498;