13-23888993-C-G

Position:

• chr13-23888993-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005932.4(MIPEP):​c.189+139G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 805,618 control chromosomes in the GnomAD database, including 7,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.12 (1147 hom., cov: 32)
  • Exomes 𝑓: 0.13 (6381 hom.)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0890

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]

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 13-23888993-C-G is Benign according to our data. Variant chr13-23888993-C-G is described in ClinVar as [Benign]. Clinvar id is 1223310.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4	c.189+139G>C		intron_variant		ENST00000382172.4	NP_005923.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIPEP	ENST00000382172.4	c.189+139G>C		intron_variant		1	NM_005932.4	ENSP00000371607.3
PCOTH	ENST00000382133.9	n.152C>G		non_coding_transcript_exon_variant	1/4	1
MIPEP	ENST00000469167.1	n.406G>C		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17840 AN: 152140 Hom.: 1146 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.0856

Gnomad ASJ AF: 0.0949

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0931

Gnomad FIN AF: 0.0802

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.109

GnomAD4 exome AF: 0.132 AC: 86215 AN: 653360 Hom.: 6381 Cov.: 9 AF XY: 0.132 AC XY: 42445 AN XY: 322742

Gnomad4 AFR exome AF: 0.116

Gnomad4 AMR exome AF: 0.0734

Gnomad4 ASJ exome AF: 0.0872

Gnomad4 EAS exome AF: 0.000408

Gnomad4 SAS exome AF: 0.0985

Gnomad4 FIN exome AF: 0.0875

Gnomad4 NFE exome AF: 0.145

Gnomad4 OTH exome AF: 0.121

GnomAD4 genome AF: 0.117 AC: 17854 AN: 152258 Hom.: 1147 Cov.: 32 AF XY: 0.115 AC XY: 8528 AN XY: 74448

Gnomad4 AFR AF: 0.113

Gnomad4 AMR AF: 0.0855

Gnomad4 ASJ AF: 0.0949

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0924

Gnomad4 FIN AF: 0.0802

Gnomad4 NFE AF: 0.143

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0657 Hom.: 69

Bravo AF: 0.115

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.4
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs17340157; hg19: chr13-24463132;