13-23760142-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 1P and 14B. PP3BP4_ModerateBP6_Very_StrongBS1

The NM_005932.4(MIPEP):c.1924G>A(p.Ala642Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000234 in 1,614,134 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00032 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 1 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 7.86

Publications

2 publications found

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 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

MIPEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

PP3

Multiple lines of computational evidence support a deleterious effect 6: AlphaMissense, Cadd, Eigen, FATHMM_MKL, MutationAssessor, phyloP100way_vertebrate [when max_spliceai, M_CAP, MetaRNN, MutationTaster was below the threshold]

BP4

Computational evidence support a benign effect (MetaRNN=0.09164819).

BP6

Variant 13-23760142-C-T is Benign according to our data. Variant chr13-23760142-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 757963.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000322 (49/152274) while in subpopulation SAS AF = 0.000414 (2/4828). AF 95% confidence interval is 0.00017. There are 1 homozygotes in GnomAd4. There are 30 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

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.1924G>A	p.Ala642Thr	missense	Exon 17 of 19	NP_005923.3	Q99797

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MIPEP	ENST00000382172.4	TSL:1 MANE Select	c.1924G>A	p.Ala642Thr	missense	Exon 17 of 19	ENSP00000371607.3	Q99797
MIPEP	ENST00000906723.1		c.1885G>A	p.Ala629Thr	missense	Exon 17 of 19	ENSP00000576782.1
MIPEP	ENST00000906727.1		c.1846G>A	p.Ala616Thr	missense	Exon 16 of 18	ENSP00000576786.1

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000461

AC:

116

AN:

251440

AF XY:

0.000427

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00715

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000132

Gnomad OTH exome

AF:

0.000978

GnomAD4 exome

AF:

0.000224

AC:

328

AN:

1461860

Hom.:

Cov.:

AF XY:

0.000246

AC XY:

179

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33480

American (AMR)

AF:

0.000492

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00750

AC:

196

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000522

AC:

AN:

1111994

Other (OTH)

AF:

0.000729

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.446

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000322

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000403

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41564

American (AMR)

AF:

0.000392

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00864

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000118

AC:

AN:

68020

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000437

Hom.:

Bravo

AF:

0.000291

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000329

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000296

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.83

BayesDel_addAF

Uncertain

0.013

BayesDel_noAF

Uncertain

0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

Eigen

Pathogenic

0.72

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

M_CAP

Benign

0.050

MetaRNN

Benign

0.092

MetaSVM

Benign

-0.62

MutationAssessor

Pathogenic

3.7

PhyloP100

7.9

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.46

Sift

Benign

0.039

Sift4G

Uncertain

0.045

Polyphen

0.99

Vest4

0.98

MVP

0.65

MPC

0.47

ClinPred

0.39

GERP RS

5.5

Varity_R

0.74

gMVP

0.84

Mutation Taster

=35/65

disease causing

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over