rs9318064

Variant names:

• chr13-23822010-A-C
• rs9318064
• NM_005932.4:c.1654-12086T>G

Your query was ambiguous. Multiple possible variants found:

• chr13-23822010-A-C
• chr13-23822010-A-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.1654-12086T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,078 control chromosomes in the GnomAD database, including 9,990 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 0.35 (9990 hom., cov: 32)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.331
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIPEP	NM_005932.4	c.1654-12086T>G		intron_variant	Intron 14 of 18	ENST00000382172.4	NP_005923.3
MIPEP	XM_011535097.3	c.1468-12086T>G		intron_variant	Intron 14 of 18		XP_011533399.1
MIPEP	XM_011535098.4	c.1654-12086T>G		intron_variant	Intron 14 of 16		XP_011533400.1
MIPEP	XM_047430368.1	c.1468-12086T>G		intron_variant	Intron 14 of 16		XP_047286324.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MIPEP	ENST00000382172.4	c.1654-12086T>G		intron_variant	Intron 14 of 18	1	NM_005932.4	ENSP00000371607.3

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53319 AN: 151960 Hom.: 9971 Cov.: 32

Gnomad AFR AF: 0.483

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.351 AC: 53378 AN: 152078 Hom.: 9990 Cov.: 32 AF XY: 0.351 AC XY: 26074 AN XY: 74350

African (AFR) AF: 0.483 AC: 20033 AN: 41468

American (AMR) AF: 0.253 AC: 3867 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1213 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1148 AN: 5184

South Asian (SAS) AF: 0.368 AC: 1773 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3212 AN: 10556

Middle Eastern (MID) AF: 0.322 AC: 94 AN: 292

European-Non Finnish (NFE) AF: 0.308 AC: 20933 AN: 67986

Other (OTH) AF: 0.333 AC: 702 AN: 2108

Alfa AF: 0.316 Hom.: 33448

Bravo AF: 0.351

Asia WGS AF: 0.300 AC: 1045 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.82
DANN	Benign	0.38
PhyloP100		-0.33
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: rs9318064; hg19: chr13-24396149;