rs6721762

Positions:

• chr2-27310751-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MPV17	NM_002437.5	c.462-770G>A		intron_variant		ENST00000380044.6
MPV17	XM_005264326.5	c.462-770G>A		intron_variant
MPV17	XM_017004151.2	c.414-770G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MPV17	ENST00000380044.6	c.462-770G>A		intron_variant		1	NM_002437.5	P1

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

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.0425

Gnomad4 ASJ AF: 0.0248

Gnomad4 EAS AF: 0.00135

Gnomad4 SAS AF: 0.0562

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0391

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0435 Hom.: 111

Bravo AF: 0.0547

Asia WGS AF: 0.0240 AC: 83 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.4
DANN	Benign	0.55

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: rs6721762; hg19: chr2-27533619;