20-17988280-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_052865.4(MGME1):c.846T>C(p.Asp282Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 1,613,072 control chromosomes in the GnomAD database, including 74,532 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6220 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68312 hom. )

Consequence

MGME1
NM_052865.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.00900

Publications

20 publications found

Variant links:

Genes affected

MGME1 (HGNC:16205): (mitochondrial genome maintenance exonuclease 1) The protein encoded by this gene is a nuclear-encoded mitochondrial protein necessary for the maintenance of mitochondrial genome synthesis. The encoded protein is a RecB-type exonuclease and primarily cleaves single-stranded DNA. Defects in this gene have been associated with mitochondrial DNA depletion syndrome-11. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

MGME1 links:

OVOL2 (HGNC:15804): (ovo like zinc finger 2) This gene encodes a member of the evolutionarily conserved ovo-like protein family. Mammalian members of this family contain a single zinc finger domain composed of a tetrad of C2H2 zinc fingers with variable N- and C-terminal extensions that contain intrinsically disordered domains. Members of this family are involved in epithelial development and differentiation. Knockout of this gene in mouse results in early embryonic lethality with phenotypes that include neurectoderm expansion, impaired vascularization, and heart anomalies. In humans, allelic variants of this gene have been associated with posterior polymorphous corneal dystrophy. [provided by RefSeq, Apr 2016]

OVOL2 Gene-Disease associations (from GenCC):

posterior polymorphous corneal dystrophy 1
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
congenital hereditary endothelial dystrophy type I
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
posterior polymorphous corneal dystrophy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

OVOL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP6

Variant 20-17988280-T-C is Benign according to our data. Variant chr20-17988280-T-C is described in ClinVar as Benign. ClinVar VariationId is 262249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.009 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGME1	NM_052865.4 link	c.846T>C	p.Asp282Asp	synonymous_variant	Exon 4 of 5	ENST00000377710.10	NP_443097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGME1	ENST00000377710.10 link	c.846T>C	p.Asp282Asp	synonymous_variant	Exon 4 of 5	1	NM_052865.4	ENSP00000366939.5

Frequencies

GnomAD3 genomes

AF:

0.280

AC:

42620

AN:

152022

Hom.:

6212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.213

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.269

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.424

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.290

Gnomad OTH

AF:

0.266

GnomAD2 exomes

AF:

0.312

AC:

78102

AN:

250724

AF XY:

0.318

show subpopulations

Gnomad AFR exome

AF:

0.212

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.334

Gnomad EAS exome

AF:

0.443

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.288

GnomAD4 exome

AF:

0.302

AC:

440913

AN:

1460932

Hom.:

68312

Cov.:

AF XY:

0.305

AC XY:

221940

AN XY:

726776

show subpopulations

African (AFR)

AF:

0.206

AC:

6893

AN:

33438

American (AMR)

AF:

0.233

AC:

10400

AN:

44638

Ashkenazi Jewish (ASJ)

AF:

0.336

AC:

8774

AN:

26110

East Asian (EAS)

AF:

0.393

AC:

15598

AN:

39648

South Asian (SAS)

AF:

0.410

AC:

35304

AN:

86110

European-Finnish (FIN)

AF:

0.340

AC:

18162

AN:

53410

Middle Eastern (MID)

AF:

0.219

AC:

1264

AN:

5766

European-Non Finnish (NFE)

AF:

0.294

AC:

326290

AN:

1111460

Other (OTH)

AF:

0.302

AC:

18228

AN:

60352

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

14158

28315

42473

56630

70788

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10936

21872

32808

43744

54680

<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:

0.280

AC:

42647

AN:

152140

Hom.:

6220

Cov.:

AF XY:

0.288

AC XY:

21389

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.213

AC:

8834

AN:

41496

American (AMR)

AF:

0.269

AC:

4103

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1150

AN:

3470

East Asian (EAS)

AF:

0.432

AC:

2235

AN:

5170

South Asian (SAS)

AF:

0.424

AC:

2046

AN:

4828

European-Finnish (FIN)

AF:

0.339

AC:

3592

AN:

10602

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.290

AC:

19750

AN:

67996

Other (OTH)

AF:

0.266

AC:

560

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1579

3158

4736

6315

7894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

438

876

1314

1752

2190

<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:

0.264

Hom.:

3525

Bravo

AF:

0.267

Asia WGS

AF:

0.412

AC:

1433

AN:

3478

EpiCase

AF:

0.280

EpiControl

AF:

0.277

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Feb 19, 2016

Mayo Clinic Laboratories, Mayo Clinic

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:2

Feb 23, 2016

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Dec 02, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

0.62

(source)

DANN

Benign

0.76

PhyloP100

-0.0090

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over