Genetic Variant MPV17L:p.Arg41Gly (chr16-15396018-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001128423.2(MPV17L):c.121C>G(p.Arg41Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000218 in 1,375,544 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MPV17L
NM_001128423.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.240

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.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.081884444).

BP6

Variant 16-15396018-C-G is Benign according to our data. Variant chr16-15396018-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2610768.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MPV17L	NM_001128423.2 link	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 4	ENST00000396385.4	NP_001121895.1	Q2QL34-1
MPV17L-BMERB1	NM_001414674.1 link	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 6		NP_001401603.1
MPV17L	NM_173803.4 link	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 3		NP_776164.2	Q2QL34-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MPV17L	ENST00000396385.4 link	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 4	1	NM_001128423.2	ENSP00000379669.3		Q2QL34-1
ENSG00000261130	ENST00000568766.1 link	c.121C>G	p.Arg41Gly	missense_variant	Exon 1 of 2	2		ENSP00000454340.1		H3BMD7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000218

AC:

AN:

1375544

Hom.:

Cov.:

AF XY:

0.00000442

AC XY:

AN XY:

678318

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30226

American (AMR)

AF:

0.00

AC:

AN:

35064

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24562

East Asian (EAS)

AF:

0.00

AC:

AN:

34896

South Asian (SAS)

AF:

0.00

AC:

AN:

77400

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37052

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4070

European-Non Finnish (NFE)

AF:

0.00000186

AC:

AN:

1074960

Other (OTH)

AF:

0.0000174

AC:

AN:

57314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Jul 11, 2023

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.017

BayesDel_noAF

Benign

-0.21

CADD

Benign

0.35

(source)

DANN

Benign

0.50

DEOGEN2

Benign

0.029

.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0080

LIST_S2

Benign

0.19

T;T;T

M_CAP

Pathogenic

0.40

MetaRNN

Benign

0.082

T;T;T

MetaSVM

Benign

-0.60

MutationAssessor

Benign

-0.92

N;N;.

PhyloP100

-0.24

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.6

N;N;N

REVEL

Uncertain

0.39

Sift

Benign

0.40

T;T;T

Sift4G

Benign

0.55

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.086

MutPred

0.46

Loss of MoRF binding (P = 0.045);Loss of MoRF binding (P = 0.045);Loss of MoRF binding (P = 0.045);

MVP

0.41

MPC

1.8

ClinPred

0.039

GERP RS

-1.4

PromoterAI

0.053

Neutral

(source)

Varity_R

0.048

gMVP

0.58

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over