13-23805994-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_005932.4(MIPEP):c.1804G>A(p.Glu602Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000952 in 1,613,936 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0051 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00052 ( 6 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008731693).

BP6

Variant 13-23805994-C-T is Benign according to our data. Variant chr13-23805994-C-T is described in ClinVar as [Benign]. Clinvar id is 784267.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00507 (772/152262) while in subpopulation AFR AF= 0.0176 (732/41554). AF 95% confidence interval is 0.0166. There are 8 homozygotes in gnomad4. There are 386 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MIPEP	NM_005932.4 linkuse as main transcript	c.1804G>A	p.Glu602Lys	missense_variant	16/19	ENST00000382172.4
MIPEP	XM_011535097.3 linkuse as main transcript	c.1618G>A	p.Glu540Lys	missense_variant	16/19
MIPEP	XM_011535098.4 linkuse as main transcript	c.1804G>A	p.Glu602Lys	missense_variant	16/17
MIPEP	XM_047430368.1 linkuse as main transcript	c.1618G>A	p.Glu540Lys	missense_variant	16/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIPEP	ENST00000382172.4 linkuse as main transcript	c.1804G>A	p.Glu602Lys	missense_variant	16/19	1	NM_005932.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00507

AC:

772

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00255

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:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00132

AC:

331

AN:

251398

Hom.:

AF XY:

0.00105

AC XY:

143

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0175

Gnomad AMR exome

AF:

0.00107

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000523

AC:

765

AN:

1461674

Hom.:

Cov.:

AF XY:

0.000474

AC XY:

345

AN XY:

727126

show subpopulations

Gnomad4 AFR exome

AF:

0.0183

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00121

GnomAD4 genome

AF:

0.00507

AC:

772

AN:

152262

Hom.:

Cov.:

AF XY:

0.00519

AC XY:

386

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0176

Gnomad4 AMR

AF:

0.00255

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000714

Hom.:

Bravo

AF:

0.00609

ESP6500AA

AF:

0.0143

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00159

AC:

193

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 15, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.21

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.86

LIST_S2

Uncertain

0.93

MetaRNN

Benign

0.0087

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.46

PROVEAN

Benign

-2.0

REVEL

Benign

0.10

Sift

Benign

0.20

Sift4G

Benign

0.46

Polyphen

0.0060

Vest4

0.62

MVP

0.32

MPC

0.13

ClinPred

0.017

GERP RS

5.7

Varity_R

0.29

gMVP

0.56

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