chr2-27309900-A-C
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Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_002437.5(MPV17):c.*12T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000918 in 1,611,112 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00078 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00093 ( 1 hom. )
Consequence
MPV17
NM_002437.5 3_prime_UTR
NM_002437.5 3_prime_UTR
Scores
1
14
Clinical Significance
Conservation
PhyloP100: -0.259
Genes affected
MPV17 (HGNC:7224): (mitochondrial inner membrane protein MPV17) This gene encodes a mitochondrial inner membrane protein that is implicated in the metabolism of reactive oxygen species. Mutations in this gene have been associated with the hepatocerebral form of mitochondrial DNA depletion syndrome (MDDS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.011353552).
BP6
Variant 2-27309900-A-C is Benign according to our data. Variant chr2-27309900-A-C is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 387355.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPV17 | NM_002437.5 | c.*12T>G | 3_prime_UTR_variant | 8/8 | ENST00000380044.6 | ||
MPV17 | XM_005264326.5 | c.*12T>G | 3_prime_UTR_variant | 8/8 | |||
MPV17 | XM_017004151.2 | c.*12T>G | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPV17 | ENST00000380044.6 | c.*12T>G | 3_prime_UTR_variant | 8/8 | 1 | NM_002437.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000782 AC: 119AN: 152200Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000916 AC: 230AN: 251030Hom.: 1 AF XY: 0.000958 AC XY: 130AN XY: 135712
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GnomAD4 exome AF: 0.000932 AC: 1360AN: 1458794Hom.: 1 Cov.: 29 AF XY: 0.000908 AC XY: 659AN XY: 725976
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GnomAD4 genome AF: 0.000781 AC: 119AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000832 AC XY: 62AN XY: 74484
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 21, 2018 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N;N;N;N
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Benign
T
Polyphen
B
Vest4
MVP
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at