MPV17 p.Arg125Arg

Variant names:

• chr2-27312493-C-C
• NM_002437.5:c.

Your query was ambiguous. Multiple possible variants found:

• chr2-27312494--
• chr2-27312494-C-A
• chr2-27312494-C-G
• chr2-27312494-C-T
• chr2-27312496-G-T
• chr2-27312494-CCG-TCT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_002437.5(MPV17):​c. variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPV17 NM_002437.5 splice_donor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.03
• Publications: 0 publications found

Genes affected

MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]

MPV17 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• mitochondrial DNA depletion syndrome 6 (hepatocerebral type)

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet
• Charcot-Marie-Tooth disease, axonal, type 2EE

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.18079096 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8.2, offset of 0 (no position change), new splice context is: cggGTgagc. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in inframe change.
• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002437.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17	NM_002437.5	MANE Select	c.		splice_donor intron	N/A	NP_002428.1	P39210

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17	ENST00000380044.6	TSL:1 MANE Select	c.		splice_donor intron	N/A	ENSP00000369383.1	P39210
	MPV17	ENST00000233545.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000233545.2	P39210
	MPV17	ENST00000403262.6	TSL:1	c.		splice_donor intron	N/A	ENSP00000385671.1	B5MCF8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-27535360;