13-23889183-G-C

Position:

• chr13-23889183-G-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2 BP4_Strong BP6_Moderate BP7 BS1

The NM_005932.4(MIPEP):​c.138C>G​(p.Ala46Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000525 in 1,466,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000029 (1 hom.)
• Consequence: MIPEP NM_005932.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.658

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 -9 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 13-23889183-G-C is Benign according to our data. Variant chr13-23889183-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2418156.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.658 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000256 (39/152328) while in subpopulation AFR AF= 0.000842 (35/41566). AF 95% confidence interval is 0.000622. There are 0 homozygotes in gnomad4. There are 17 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MIPEP	NM_005932.4	c.138C>G	p.Ala46Ala	synonymous_variant	1/19	ENST00000382172.4	NP_005923.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MIPEP	ENST00000382172.4	c.138C>G	p.Ala46Ala	synonymous_variant	1/19	1	NM_005932.4	ENSP00000371607.3
PCOTH	ENST00000382133.9	n.170+172G>C		intron_variant		1
MIPEP	ENST00000469167.1	n.216C>G		non_coding_transcript_exon_variant	1/3	5

Frequencies

GnomAD3 genomes AF: 0.000256 AC: 39 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000845

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD4 exome AF: 0.0000289 AC: 38 AN: 1314524 Hom.: 1 Cov.: 30 AF XY: 0.0000217 AC XY: 14 AN XY: 646520

Gnomad4 AFR exome AF: 0.000811

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000432

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000384

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome AF: 0.000256 AC: 39 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74474

Gnomad4 AFR AF: 0.000842

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000945

Bravo AF: 0.000223

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	13
DANN	Benign	0.91

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

Other links and lift over

dbSNP: rs371260499; hg19: chr13-24463322;