rs73901138

Variant names:

• chr20-17969103-C-T
• rs73901138
• NM_052865.4:c.-98C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-17969103-C-T
• chr20-17969103-C-A
• chr20-17969103-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_052865.4(MGME1):​c.-98C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 152,332 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (32 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MGME1 NM_052865.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• Publications: 2 publications found

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]

SNX5 (HGNC:14969): (sorting nexin 5) This gene encodes a member of the sorting nexin family. Members of this family contain a phox (PX) domain, which is a phosphoinositide binding domain, and are involved in intracellular trafficking. This protein functions in endosomal sorting, the phosphoinositide-signaling pathway, and macropinocytosis. This gene may play a role in the tumorigenesis of papillary thyroid carcinoma. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 20-17969103-C-T is Benign according to our data. Variant chr20-17969103-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1329826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0119 (1806/152332) while in subpopulation AFR AF = 0.0397 (1649/41570). AF 95% confidence interval is 0.0381. There are 32 homozygotes in GnomAd4. There are 885 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052865.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGME1	NM_052865.4	MANE Select	c.-98C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	NP_443097.1	Q9BQP7
	MGME1	NM_052865.4	MANE Select	c.-98C>T		5_prime_UTR	Exon 1 of 5	NP_443097.1	Q9BQP7
	MGME1	NM_001310338.2		c.-98C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	NP_001297267.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MGME1	ENST00000377710.10	TSL:1 MANE Select	c.-98C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000366939.5	Q9BQP7
	MGME1	ENST00000377710.10	TSL:1 MANE Select	c.-98C>T		5_prime_UTR	Exon 1 of 5	ENSP00000366939.5	Q9BQP7
	MGME1	ENST00000948799.1		c.-98C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 6	ENSP00000618858.1

Frequencies

GnomAD3 genomes AF: 0.0118 AC: 1791 AN: 152216 Hom.: 31 Cov.: 33

Gnomad AFR AF: 0.0394

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00765

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0124

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 196 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 158

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 126

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0119 AC: 1806 AN: 152332 Hom.: 32 Cov.: 33 AF XY: 0.0119 AC XY: 885 AN XY: 74490

African (AFR) AF: 0.0397 AC: 1649 AN: 41570

American (AMR) AF: 0.00764 AC: 117 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00374 Hom.: 0

Bravo AF: 0.0134

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.77
DANN	Benign	0.85
PhyloP100		-2.2
PromoterAI		0.13	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=299/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs73901138; hg19: chr20-17949746;