rs6721762

Variant names:

• chr2-27310751-C-T
• rs6721762
• NM_002437.5:c.462-770G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002437.5(MPV17):​c.462-770G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,038 control chromosomes in the GnomAD database, including 261 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 0.051 (261 hom., cov: 32)
• Consequence: MPV17 NM_002437.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40
• Publications: 3 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: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Charcot-Marie-Tooth disease, axonal, type 2EE

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0874 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17	NM_002437.5	MANE Select	c.462-770G>A		intron	N/A	NP_002428.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MPV17	ENST00000380044.6	TSL:1 MANE Select	c.462-770G>A		intron	N/A	ENSP00000369383.1
	MPV17	ENST00000233545.6	TSL:1	c.462-770G>A		intron	N/A	ENSP00000233545.2
	MPV17	ENST00000405983.5	TSL:5	c.507-770G>A		intron	N/A	ENSP00000384586.1

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7790 AN: 151920 Hom.: 261 Cov.: 32

Gnomad AFR AF: 0.0902

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0425

Gnomad ASJ AF: 0.0248

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.0525

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

GnomAD4 genome AF: 0.0512 AC: 7785 AN: 152038 Hom.: 261 Cov.: 32 AF XY: 0.0488 AC XY: 3627 AN XY: 74296

African (AFR) AF: 0.0898 AC: 3728 AN: 41492

American (AMR) AF: 0.0425 AC: 649 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0248 AC: 86 AN: 3468

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5176

South Asian (SAS) AF: 0.0562 AC: 271 AN: 4818

European-Finnish (FIN) AF: 0.0157 AC: 165 AN: 10530

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2656 AN: 67958

Other (OTH) AF: 0.0520 AC: 110 AN: 2116

Alfa AF: 0.0487 Hom.: 253

Bravo AF: 0.0547

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6721762; hg19: chr2-27533619;