13-23889137-G-A

Position:

chr13-23889137-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1

The NM_005932.4(MIPEP):c.184C>T(p.Arg62Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000346 in 1,422,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.59

Variant links:

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 links:

PCOTH (HGNC:39839): (prostate and testis expressed opposite C1QTNF9B and MIPEP) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PCOTH links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.004468143).

BP6

Variant 13-23889137-G-A is Benign according to our data. Variant chr13-23889137-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 709907.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00179 (272/152332) while in subpopulation AFR AF= 0.00635 (264/41580). AF 95% confidence interval is 0.00572. There are 1 homozygotes in gnomad4. There are 141 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4 link	c.184C>T	p.Arg62Cys	missense_variant	1/19	ENST00000382172.4	NP_005923.3	Q99797

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIPEP	ENST00000382172.4 link	c.184C>T	p.Arg62Cys	missense_variant	1/19	1	NM_005932.4	ENSP00000371607.3	Q99797
PCOTH	ENST00000382133.9 link	n.170+126G>A		intron_variant		1
MIPEP	ENST00000469167.1 link	n.262C>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

AF:

0.00179

AC:

272

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00637

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000172

AC:

AN:

40608

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

22566

show subpopulations

Gnomad AFR exome

AF:

0.00441

Gnomad AMR exome

AF:

0.000374

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

221

AN:

1270612

Hom.:

Cov.:

AF XY:

0.000166

AC XY:

103

AN XY:

621542

show subpopulations

Gnomad4 AFR exome

AF:

0.00692

Gnomad4 AMR exome

AF:

0.000445

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000245

Gnomad4 OTH exome

AF:

0.000349

GnomAD4 genome

AF:

0.00179

AC:

272

AN:

152332

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00635

Gnomad4 AMR

AF:

0.000457

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000172

Hom.:

Bravo

AF:

0.00212

ESP6500AA

AF:

0.00359

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000205

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 19, 2022	- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 23, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

MIPEP-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Feb 18, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.38

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.0045

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.1

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.12

Sift

Benign

0.037

Sift4G

Uncertain

0.038

Polyphen

0.70

Vest4

0.28

MVP

0.40

MPC

0.25

ClinPred

0.14

GERP RS

4.3

Varity_R

0.27

gMVP

0.46

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over