Variant chr13-23889275-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005932.4(MIPEP):c.46G>T(p.Ala16Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 1,378,908 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0053 ( 9 hom., cov: 32)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

MIPEP
NM_005932.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.14

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:

PCOTH (HGNC:39839): (prostate and testis expressed opposite C1QTNF9B and MIPEP) Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

PCOTH 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=0.003097713).

BP6

Variant 13-23889275-C-A is Benign according to our data. Variant chr13-23889275-C-A is described in ClinVar as [Benign]. Clinvar id is 787409.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00528 (805/152330) while in subpopulation AFR AF= 0.0189 (784/41590). AF 95% confidence interval is 0.0178. There are 9 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4 link	c.46G>T	p.Ala16Ser	missense_variant	1/19	ENST00000382172.4	NP_005923.3	Q99797

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIPEP	ENST00000382172.4 link	c.46G>T	p.Ala16Ser	missense_variant	1/19	1	NM_005932.4	ENSP00000371607.3	Q99797
PCOTH	ENST00000382133.9 link	n.170+264C>A		intron_variant		1
MIPEP	ENST00000469167.1 link	n.124G>T		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes

AF:

0.00524

AC:

798

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0187

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000851

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:

0.00382

GnomAD3 exomes

AF:

0.000638

AC:

AN:

15664

Hom.:

AF XY:

0.000371

AC XY:

AN XY:

8076

show subpopulations

Gnomad AFR exome

AF:

0.0294

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.000501

AC:

615

AN:

1226578

Hom.:

Cov.:

AF XY:

0.000448

AC XY:

266

AN XY:

593998

show subpopulations

Gnomad4 AFR exome

AF:

0.0210

Gnomad4 AMR exome

AF:

0.00120

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000366

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.00175

GnomAD4 genome

AF:

0.00528

AC:

805

AN:

152330

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

372

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.0189

Gnomad4 AMR

AF:

0.000849

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:

0.00378

Alfa

AF:

0.000160

Hom.:

Bravo

AF:

0.00605

ExAC

AF:

0.000660

AC:

Asia WGS

AF:

0.00231

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Nov 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.032

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0031

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-0.23

REVEL

Benign

0.034

Sift

Benign

0.070

Sift4G

Benign

0.091

Polyphen

0.041

Vest4

0.25

MVP

0.27

MPC

0.082

ClinPred

0.025

GERP RS

2.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.087

gMVP

0.40

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