rs779425887

Variant names:

• chr2-27309916-A-C
• rs779425887
• NM_002437.5:c.527T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-27309916-A-C
• chr2-27309916-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 4P and 2B. PM1 PM2 BP4_Moderate

The NM_002437.5(MPV17):​c.527T>G​(p.Leu176Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign 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. L176P) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MPV17 NM_002437.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• 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: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• Charcot-Marie-Tooth disease, axonal, type 2EE

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM1: In a chain Mitochondrial inner membrane protein Mpv17 (size 175) in uniprot entity MPV17_HUMAN there are 23 pathogenic changes around while only 5 benign (82%) in NM_002437.5
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13392574).

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.527T>G	p.Leu176Arg	missense	Exon 8 of 8	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.527T>G	p.Leu176Arg	missense	Exon 8 of 8	ENSP00000369383.1	P39210
	MPV17	ENST00000233545.6	TSL:1	c.527T>G	p.Leu176Arg	missense	Exon 7 of 7	ENSP00000233545.2	P39210
	MPV17	ENST00000911060.1		c.677T>G	p.Leu226Arg	missense	Exon 10 of 10	ENSP00000581119.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	18
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.6
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.040	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.0	B
Vest4		0.15
MutPred		0.53		Loss of stability (P = 0.0083)
MVP		0.33
MPC		0.94
ClinPred		0.35	T
GERP RS		0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.32
Mutation Taster		=86/14	polymorphism

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: rs779425887; hg19: chr2-27532784;