rs9318086

Variant names:

• chr13-23858328-A-G
• rs9318086
• NM_005932.4:c.1106+532T>C

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+532T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.555 in 151,788 control chromosomes in the GnomAD database, including 23,515 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 0.55 (23515 hom., cov: 30)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0300
• Publications: 25 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: Labcorp Genetics (formerly Invitae), Orphanet, Broad Center for Mendelian Genomics
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.701 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIPEP	NM_005932.4	c.1106+532T>C		intron_variant	Intron 10 of 18	ENST00000382172.4	NP_005923.3
MIPEP	XM_011535097.3	c.920+532T>C		intron_variant	Intron 10 of 18		XP_011533399.1
MIPEP	XM_011535098.4	c.1106+532T>C		intron_variant	Intron 10 of 16		XP_011533400.1
MIPEP	XM_047430368.1	c.920+532T>C		intron_variant	Intron 10 of 16		XP_047286324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIPEP	ENST00000382172.4	c.1106+532T>C		intron_variant	Intron 10 of 18	1	NM_005932.4	ENSP00000371607.3
MIPEP	ENST00000494139.1	n.503+532T>C		intron_variant	Intron 5 of 5	2

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84087 AN: 151672 Hom.: 23486 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.593

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.540

Gnomad OTH AF: 0.550

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

GnomAD4 genome AF: 0.555 AC: 84168 AN: 151788 Hom.: 23515 Cov.: 30 AF XY: 0.555 AC XY: 41204 AN XY: 74182

African (AFR) AF: 0.563 AC: 23266 AN: 41340

American (AMR) AF: 0.594 AC: 9058 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1904 AN: 3472

East Asian (EAS) AF: 0.543 AC: 2799 AN: 5156

South Asian (SAS) AF: 0.721 AC: 3468 AN: 4808

European-Finnish (FIN) AF: 0.497 AC: 5229 AN: 10524

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.540 AC: 36698 AN: 67924

Other (OTH) AF: 0.555 AC: 1169 AN: 2106

Alfa AF: 0.547 Hom.: 104181

Bravo AF: 0.556

Asia WGS AF: 0.659 AC: 2293 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.92
DANN	Benign	0.65
PhyloP100		-0.030
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: rs9318086; hg19: chr13-24432467;