rs537985967

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_005932.4(MIPEP):​c.2080G>C​(p.Val694Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,460,426 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V694I) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

1
5
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.71

Publications

1 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: Labcorp Genetics (formerly Invitae), Orphanet, Broad Center for Mendelian Genomics
  • mitochondrial disease
    Inheritance: AR Classification: MODERATE Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MIPEPNM_005932.4 linkc.2080G>C p.Val694Leu missense_variant Exon 19 of 19 ENST00000382172.4 NP_005923.3 Q99797
MIPEPXM_011535097.3 linkc.1894G>C p.Val632Leu missense_variant Exon 19 of 19 XP_011533399.1
LOC105370113XR_007063722.1 linkn.651+1133C>G intron_variant Intron 1 of 1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MIPEPENST00000382172.4 linkc.2080G>C p.Val694Leu missense_variant Exon 19 of 19 1 NM_005932.4 ENSP00000371607.3 Q99797

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00000401
AC:
1
AN:
249256
AF XY:
0.00
show subpopulations
Gnomad AFR exome
AF:
0.0000620
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS 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:
0.00000274
AC:
4
AN:
1460426
Hom.:
0
Cov.:
29
AF XY:
0.00000275
AC XY:
2
AN XY:
726514
show subpopulations
African (AFR)
AF:
0.0000299
AC:
1
AN:
33416
American (AMR)
AF:
0.00
AC:
0
AN:
44720
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26130
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39570
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86106
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53334
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000270
AC:
3
AN:
1111054
Other (OTH)
AF:
0.00
AC:
0
AN:
60328
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.65
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.35
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.041
T
Eigen
Benign
0.037
Eigen_PC
Benign
0.16
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.59
D
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
2.0
M
PhyloP100
5.7
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.26
Sift
Benign
0.056
T
Sift4G
Benign
0.080
T
Polyphen
0.16
B
Vest4
0.73
MutPred
0.48
Gain of disorder (P = 0.1621);
MVP
0.41
MPC
0.25
ClinPred
0.50
D
GERP RS
5.4
Varity_R
0.45
gMVP
0.55
Mutation Taster
=80/20
polymorphism

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

Publications

Other links and lift over

dbSNP: rs537985967; hg19: chr13-24304549; COSMIC: COSV105928389; API