chr13-23854958-C-A

Variant names:

• chr13-23854958-C-A
• rs9507174
• NM_005932.4:c.1106+3902G>T

Variant summary

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

The NM_005932.4(MIPEP):​c.1106+3902G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 151,282 control chromosomes in the GnomAD database, including 16,973 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 0.47 (16973 hom., cov: 31)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 2 publications found

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]

MIPEP Gene-Disease associations (from GenCC):

• lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Broad Center for Mendelian Genomics, Labcorp Genetics (formerly Invitae), Orphanet
• mitochondrial disease

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005932.4. 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
	MIPEP	NM_005932.4	MANE Select	c.1106+3902G>T		intron	N/A	NP_005923.3	Q99797

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIPEP	ENST00000382172.4	TSL:1 MANE Select	c.1106+3902G>T		intron	N/A	ENSP00000371607.3	Q99797
	MIPEP	ENST00000906723.1		c.1067+3902G>T		intron	N/A	ENSP00000576782.1
	MIPEP	ENST00000906727.1		c.1106+3902G>T		intron	N/A	ENSP00000576786.1

Frequencies

GnomAD3 genomes AF: 0.467 AC: 70616 AN: 151174 Hom.: 16968 Cov.: 31

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.395

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.523

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.467 AC: 70661 AN: 151282 Hom.: 16973 Cov.: 31 AF XY: 0.467 AC XY: 34510 AN XY: 73872

African (AFR) AF: 0.367 AC: 15150 AN: 41238

American (AMR) AF: 0.424 AC: 6453 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.516 AC: 1787 AN: 3464

East Asian (EAS) AF: 0.396 AC: 2028 AN: 5124

South Asian (SAS) AF: 0.556 AC: 2664 AN: 4792

European-Finnish (FIN) AF: 0.538 AC: 5545 AN: 10300

Middle Eastern (MID) AF: 0.514 AC: 148 AN: 288

European-Non Finnish (NFE) AF: 0.523 AC: 35453 AN: 67832

Other (OTH) AF: 0.485 AC: 1021 AN: 2106

Alfa AF: 0.496 Hom.: 12405

Bravo AF: 0.453

Asia WGS AF: 0.520 AC: 1807 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.8
DANN	Benign	0.69
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9507174; hg19: chr13-24429097;