rs11551768

Variant names:

• chr20-17969902-A-G
• NM_052865.4:c.43A>G

Your query was ambiguous. Multiple possible variants found:

• chr20-17969902-A-G
• chr20-17969902-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_052865.4(MGME1):​c.43A>G​(p.Ser15Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MGME1 NM_052865.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.680

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]

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.065339446).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MGME1	NM_052865.4	c.43A>G	p.Ser15Gly	missense_variant	Exon 2 of 5	ENST00000377710.10	NP_443097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MGME1	ENST00000377710.10	c.43A>G	p.Ser15Gly	missense_variant	Exon 2 of 5	1	NM_052865.4	ENSP00000366939.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461284 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727000

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	9.2
DANN	Benign	0.88
DEOGEN2	Benign	0.010	T;T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.076	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.065	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	M;.;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.6	N;N;N
REVEL	Benign	0.038
Sift	Benign	0.12	T;T;T
Sift4G	Benign	0.18	T;T;T
Polyphen		0.15	B;.;.
Vest4		0.14
MutPred		0.24		Loss of disorder (P = 0.0276);Loss of disorder (P = 0.0276);Loss of disorder (P = 0.0276);
MVP		0.17
MPC		0.090
ClinPred		0.13	T
GERP RS		-0.89
Varity_R		0.063
gMVP		0.062

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr20-17950545;