Genetic Variant MPV17L:p.Met131Arg (chr16-15407834-T-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001128423.2(MPV17L):c.392T>G(p.Met131Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000155 in 1,612,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

Publications

0 publications found

Variant links:

Genes affected

MPV17L (HGNC:26827): (MPV17 mitochondrial inner membrane protein like) Involved in negative regulation of hydrogen peroxide biosynthetic process; negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; and reactive oxygen species metabolic process. Located in peroxisome. [provided by Alliance of Genome Resources, Apr 2022]

MPV17L links:

ENSG00000261130 (HGNC:):

ENSG00000261130 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16087362).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001128423.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPV17L	NM_001128423.2	MANE Select	c.392T>G	p.Met131Arg	missense	Exon 3 of 4	NP_001121895.1	Q2QL34-1
MPV17L	NM_173803.4		c.321T>G	p.Asp107Glu	missense	Exon 2 of 3	NP_776164.2	Q2QL34-2
MPV17L-BMERB1	NM_001414674.1		c.310+11627T>G		intron	N/A	NP_001401603.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MPV17L	ENST00000396385.4	TSL:1 MANE Select	c.392T>G	p.Met131Arg	missense	Exon 3 of 4	ENSP00000379669.3	Q2QL34-1
MPV17L	ENST00000287594.7	TSL:1	c.321T>G	p.Asp107Glu	missense	Exon 2 of 3	ENSP00000287594.6	Q2QL34-2
ENSG00000261130	ENST00000568766.1	TSL:2	c.310+11627T>G		intron	N/A	ENSP00000454340.1	H3BMD7

Frequencies

GnomAD3 genomes

AF:

0.0000922

AC:

AN:

151762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000339

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

250622

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1460902

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

726732

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33396

American (AMR)

AF:

0.0000224

AC:

AN:

44556

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39690

South Asian (SAS)

AF:

0.00

AC:

AN:

85962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111702

Other (OTH)

AF:

0.00

AC:

AN:

60322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000922

AC:

AN:

151762

Hom.:

Cov.:

AF XY:

0.0000540

AC XY:

AN XY:

74080

show subpopulations

African (AFR)

AF:

0.000339

AC:

AN:

41276

American (AMR)

AF:

0.00

AC:

AN:

15212

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10520

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000452

Hom.:

Bravo

AF:

0.000147

ESP6500AA

AF:

0.000683

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

(source)

DANN

Uncertain

0.98

Eigen

Benign

0.18

Eigen_PC

Benign

0.15

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.19

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Uncertain

0.10

PhyloP100

4.9

PROVEAN

Benign

-0.48

REVEL

Uncertain

0.30

Sift

Benign

0.18

Sift4G

Benign

0.49

Polyphen

0.062

Vest4

0.48

MutPred

0.46

Loss of catalytic residue at A110 (P = 0.3156)

MVP

0.29

ClinPred

0.32

GERP RS

4.8

Varity_R

0.79

Mutation Taster

=61/39

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over