Variant chr13-23756614-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005932.4(MIPEP):c.1975G>T(p.Ala659Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,612,674 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.27

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16498905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4 linkuse as main transcript	c.1975G>T	p.Ala659Ser	missense_variant	18/19	ENST00000382172.4	NP_005923.3
MIPEP	XM_011535097.3 linkuse as main transcript	c.1789G>T	p.Ala597Ser	missense_variant	18/19		XP_011533399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MIPEP	ENST00000382172.4 linkuse as main transcript	c.1975G>T	p.Ala659Ser	missense_variant	18/19	1	NM_005932.4	ENSP00000371607	P1
MIPEP	ENST00000433710.2 linkuse as main transcript	n.168G>T		non_coding_transcript_exon_variant	3/4	3
MIPEP	ENST00000464194.3 linkuse as main transcript	n.217G>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000525

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00000685

AC:

AN:

1460424

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

726624

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000193

Gnomad4 AMR

AF:

0.00

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:

0.00

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1975G>T (p.A659S) alteration is located in exon 18 (coding exon 18) of the MIPEP gene. This alteration results from a G to T substitution at nucleotide position 1975, causing the alanine (A) at amino acid position 659 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.036

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0042

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

MutationTaster

Benign

0.52

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.63

REVEL

Benign

0.015

Sift

Benign

0.31

Sift4G

Benign

0.71

Polyphen

0.0080

Vest4

0.39

MVP

0.34

MPC

0.088

ClinPred

0.11

GERP RS

2.4

Varity_R

0.051

gMVP

0.51

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