chr13-23835918-A-T

Variant names:

• chr13-23835918-A-T
• rs9551012
• NM_005932.4:c.1653+322T>A

Variant summary

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

The NM_005932.4(MIPEP):​c.1653+322T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 152,136 control chromosomes in the GnomAD database, including 4,311 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 0.20 (4311 hom., cov: 32)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 3 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MIPEP	NM_005932.4	c.1653+322T>A		intron_variant	Intron 14 of 18	ENST00000382172.4	NP_005923.3
MIPEP	XM_011535097.3	c.1467+322T>A		intron_variant	Intron 14 of 18		XP_011533399.1
MIPEP	XM_011535098.4	c.1653+322T>A		intron_variant	Intron 14 of 16		XP_011533400.1
MIPEP	XM_047430368.1	c.1467+322T>A		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.1653+322T>A		intron_variant	Intron 14 of 18	1	NM_005932.4	ENSP00000371607.3

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30067 AN: 152018 Hom.: 4296 Cov.: 32

Gnomad AFR AF: 0.398

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.194

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.162

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

GnomAD4 genome AF: 0.198 AC: 30132 AN: 152136 Hom.: 4311 Cov.: 32 AF XY: 0.198 AC XY: 14739 AN XY: 74384

African (AFR) AF: 0.398 AC: 16502 AN: 41472

American (AMR) AF: 0.132 AC: 2017 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 444 AN: 3472

East Asian (EAS) AF: 0.221 AC: 1143 AN: 5176

South Asian (SAS) AF: 0.194 AC: 935 AN: 4816

European-Finnish (FIN) AF: 0.134 AC: 1422 AN: 10588

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7174 AN: 68006

Other (OTH) AF: 0.165 AC: 349 AN: 2116

Alfa AF: 0.0691 Hom.: 102

Bravo AF: 0.206

Asia WGS AF: 0.217 AC: 755 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.34
DANN	Benign	0.50
PhyloP100		-1.8
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: rs9551012; hg19: chr13-24410057;