Variant chr20-17969679-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_052865.4(MGME1):c.-59-122C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0033 in 599,586 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0094 ( 17 hom., cov: 33)

Exomes 𝑓: 0.0012 ( 8 hom. )

Consequence

MGME1
NM_052865.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.272

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 20-17969679-C-T is Benign according to our data. Variant chr20-17969679-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1213093.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00938 (1428/152248) while in subpopulation AFR AF= 0.0324 (1345/41540). AF 95% confidence interval is 0.0309. There are 17 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MGME1	NM_052865.4 linkuse as main transcript	c.-59-122C>T		intron_variant		ENST00000377710.10

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MGME1	ENST00000377710.10 linkuse as main transcript	c.-59-122C>T	intron_variant	1	NM_052865.4	P1
MGME1	ENST00000377704.4 linkuse as main transcript	c.-59-122C>T	intron_variant	3
MGME1	ENST00000377709.1 linkuse as main transcript	c.-59-122C>T	intron_variant	2
OVOL2	ENST00000486776.5 linkuse as main transcript	n.492-12642G>A	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00938

AC:

1427

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0324

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00301

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00669

GnomAD4 exome

AF:

0.00123

AC:

549

AN:

447338

Hom.:

AF XY:

0.00108

AC XY:

252

AN XY:

232554

show subpopulations

Gnomad4 AFR exome

AF:

0.0312

Gnomad4 AMR exome

AF:

0.00178

Gnomad4 ASJ exome

AF:

0.00313

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000120

Gnomad4 OTH exome

AF:

0.00227

GnomAD4 genome

AF:

0.00938

AC:

1428

AN:

152248

Hom.:

Cov.:

AF XY:

0.00929

AC XY:

692

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0324

Gnomad4 AMR

AF:

0.00301

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00791

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.4

DANN

Benign

0.90

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over