Variant 13-23730353-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005932.4(MIPEP):c.2137G>A(p.Glu713Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,606,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.666

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.047055244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MIPEP	NM_005932.4 linkuse as main transcript	c.2137G>A	p.Glu713Lys	missense_variant	19/19	ENST00000382172.4
LOC105370113	XR_007063722.1 linkuse as main transcript	n.651+1076C>T		intron_variant, non_coding_transcript_variant
MIPEP	XM_011535097.3 linkuse as main transcript	c.1951G>A	p.Glu651Lys	missense_variant	19/19

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
MIPEP	ENST00000382172.4 linkuse as main transcript	c.2137G>A	p.Glu713Lys	missense_variant	19/19	1	NM_005932.4	P1
	ENST00000691844.2 linkuse as main transcript	n.385-4194C>T		intron_variant, non_coding_transcript_variant
MIPEP	ENST00000433710.2 linkuse as main transcript	n.330G>A		non_coding_transcript_exon_variant	4/4	3
MIPEP	ENST00000464194.3 linkuse as main transcript	n.379G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000284

AC:

AN:

246770

Hom.:

AF XY:

0.0000375

AC XY:

AN XY:

133478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000200

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000117

AC:

AN:

1454398

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

723788

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000187

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152276

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000508

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Lethal left ventricular non-compaction-seizures-hypotonia-cataract-developmental delay syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Revvity Omics, Revvity

Feb 01, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.026

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.84

M_CAP

Benign

0.0042

MetaRNN

Benign

0.047

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

MutationTaster

Benign

0.76

PrimateAI

Benign

0.33

PROVEAN

Benign

0.0

REVEL

Benign

0.046

Sift

Benign

0.33

Sift4G

Benign

0.093

Polyphen

0.0010

Vest4

0.20

MutPred

0.27

Gain of helix (P = 0.0078);

MVP

0.20

MPC

0.10

ClinPred

0.075

GERP RS

1.1

Varity_R

0.029

gMVP

0.64

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

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