rs121909721

Variant names:

• chr2-27313031-C-G
• NM_002437.5:c.149G>C

Your query was ambiguous. Multiple possible variants found:

• chr2-27313031-C-G
• chr2-27313031-C-T

Variant summary

Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PM1 PM2 PM5 PP3_Strong

The NM_002437.5(MPV17):​c.149G>C​(p.Arg50Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R50W) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPV17 NM_002437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.46

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 Pathogenic. Variant got 10 ACMG points.

• PM1: In a chain Protein Mpv17 (size 175) in uniprot entity MPV17_HUMAN there are 13 pathogenic changes around while only 1 benign (93%) in NM_002437.5
• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr2-27313032-G-A is described in Lovd as [Pathogenic].
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.981

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPV17	NM_002437.5	c.149G>C	p.Arg50Pro	missense_variant	Exon 3 of 8	ENST00000380044.6	NP_002428.1
MPV17	XM_005264326.5	c.149G>C	p.Arg50Pro	missense_variant	Exon 3 of 8		XP_005264383.1
MPV17	XM_017004151.2	c.101G>C	p.Arg34Pro	missense_variant	Exon 3 of 8		XP_016859640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPV17	ENST00000380044.6	c.149G>C	p.Arg50Pro	missense_variant	Exon 3 of 8	1	NM_002437.5	ENSP00000369383.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.53	D
BayesDel_noAF	Pathogenic	0.53
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.75	D;.;D;T;D;T;.
Eigen	Pathogenic	0.91
Eigen_PC	Pathogenic	0.82
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	.;D;D;D;D;D;D
M_CAP	Pathogenic	0.66	D
MetaRNN	Pathogenic	0.98	D;D;D;D;D;D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Pathogenic	3.7	H;.;H;.;.;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.8	D;D;D;D;D;D;D
REVEL	Pathogenic	0.92
Sift	Pathogenic	0.0	D;D;D;D;T;D;D
Sift4G	Uncertain	0.0080	D;D;D;D;D;D;.
Polyphen		1.0	D;D;D;.;.;.;.
Vest4		0.97
MutPred		0.91		Loss of helix (P = 0.079);Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;Loss of helix (P = 0.079);Loss of helix (P = 0.079);.;
MVP		0.98
MPC		1.2
ClinPred		1.0	D
GERP RS		5.4
Varity_R		0.94
gMVP		0.99

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-27535898;