chr2-27309683-A-G
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_002437.5(MPV17):c.*229T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000633 in 622,260 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.0018 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
MPV17
NM_002437.5 3_prime_UTR
NM_002437.5 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.350
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 Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BP6
Variant 2-27309683-A-G is Benign according to our data. Variant chr2-27309683-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 897342.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00177 (270/152264) while in subpopulation AFR AF= 0.00616 (256/41544). AF 95% confidence interval is 0.00554. There are 2 homozygotes in gnomad4. There are 130 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MPV17 | NM_002437.5 | c.*229T>C | 3_prime_UTR_variant | 8/8 | ENST00000380044.6 | ||
MPV17 | XM_005264326.5 | c.*229T>C | 3_prime_UTR_variant | 8/8 | |||
MPV17 | XM_017004151.2 | c.*229T>C | 3_prime_UTR_variant | 8/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MPV17 | ENST00000380044.6 | c.*229T>C | 3_prime_UTR_variant | 8/8 | 1 | NM_002437.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00177 AC: 270AN: 152146Hom.: 2 Cov.: 32
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GnomAD4 exome AF: 0.000264 AC: 124AN: 469996Hom.: 0 Cov.: 0 AF XY: 0.000222 AC XY: 55AN XY: 248012
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GnomAD4 genome AF: 0.00177 AC: 270AN: 152264Hom.: 2 Cov.: 32 AF XY: 0.00175 AC XY: 130AN XY: 74460
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Mitochondrial DNA depletion syndrome 6 (hepatocerebral type) Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at