Variant chr13-23756612-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_005932.4(MIPEP):c.1977C>T(p.Ala659Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00741 in 1,612,656 control chromosomes in the GnomAD database, including 70 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 6 hom., cov: 33)

Exomes 𝑓: 0.0074 ( 64 hom. )

Consequence

MIPEP
NM_005932.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.327

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 13-23756612-G-A is Benign according to our data. Variant chr13-23756612-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 770419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.327 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00777 (1183/152304) while in subpopulation AMR AF= 0.011 (168/15294). AF 95% confidence interval is 0.00963. There are 6 homozygotes in gnomad4. There are 542 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4 link	c.1977C>T	p.Ala659Ala	synonymous_variant	18/19	ENST00000382172.4	NP_005923.3	Q99797
MIPEP	XM_011535097.3 link	c.1791C>T	p.Ala597Ala	synonymous_variant	18/19		XP_011533399.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
MIPEP	ENST00000382172.4 link	c.1977C>T	p.Ala659Ala	synonymous_variant	18/19	1	NM_005932.4	ENSP00000371607.3	Q99797
MIPEP	ENST00000433710.2 link	n.170C>T		non_coding_transcript_exon_variant	3/4	3
MIPEP	ENST00000464194.3 link	n.219C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.00772

AC:

1175

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00835

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0111

Gnomad ASJ

AF:

0.00260

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00332

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00870

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00623

AC:

1558

AN:

250222

Hom.:

AF XY:

0.00653

AC XY:

884

AN XY:

135374

show subpopulations

Gnomad AFR exome

AF:

0.00838

Gnomad AMR exome

AF:

0.00844

Gnomad ASJ exome

AF:

0.00447

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00372

Gnomad FIN exome

AF:

0.00116

Gnomad NFE exome

AF:

0.00798

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00737

AC:

10762

AN:

1460352

Hom.:

Cov.:

AF XY:

0.00737

AC XY:

5354

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00804

Gnomad4 AMR exome

AF:

0.00780

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00318

Gnomad4 FIN exome

AF:

0.00121

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.00755

GnomAD4 genome

AF:

0.00777

AC:

1183

AN:

152304

Hom.:

Cov.:

AF XY:

0.00728

AC XY:

542

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00847

Gnomad4 AMR

AF:

0.0110

Gnomad4 ASJ

AF:

0.00260

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00374

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00872

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00766

Hom.:

Bravo

AF:

0.00835

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jul 01, 2024	MIPEP: BP4, BP7, BS2 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 12, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.10

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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