rs3794338

Positions:

• chr13-23859152-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005932.4(MIPEP):​c.1054-240G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0252 in 152,206 control chromosomes in the GnomAD database, including 371 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.025 (371 hom., cov: 33)
• Consequence: MIPEP NM_005932.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MIPEP	NM_005932.4	c.1054-240G>A		intron_variant		ENST00000382172.4
MIPEP	XM_011535097.3	c.868-240G>A		intron_variant
MIPEP	XM_011535098.4	c.1054-240G>A		intron_variant
MIPEP	XM_047430368.1	c.868-240G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MIPEP	ENST00000382172.4	c.1054-240G>A		intron_variant		1	NM_005932.4	P1
MIPEP	ENST00000494139.1	n.451-240G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0253 AC: 3844 AN: 152088 Hom.: 375 Cov.: 33

Gnomad AFR AF: 0.00454

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.0221

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00881

Gnomad OTH AF: 0.0172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0252 AC: 3836 AN: 152206 Hom.: 371 Cov.: 33 AF XY: 0.0282 AC XY: 2095 AN XY: 74418

Gnomad4 AFR AF: 0.00453

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.0294

Gnomad4 FIN AF: 0.0221

Gnomad4 NFE AF: 0.00881

Gnomad4 OTH AF: 0.0171

Alfa AF: 0.0147 Hom.: 100

Bravo AF: 0.0309

Asia WGS AF: 0.136 AC: 471 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.57

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

Other links and lift over

dbSNP: rs3794338; hg19: chr13-24433291;