rs201950015
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4BP6_Very_StrongBA1
The ENST00000387416.2(MT-TS1):n.39G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★★).
Frequency
Mitomap GenBank:
𝑓 0.013 ( AC: 805 )
Consequence
MT-TS1
ENST00000387416.2 non_coding_transcript_exon
ENST00000387416.2 non_coding_transcript_exon
Scores
Mitotip
Benign
Clinical Significance
No linked disesase in Mitomap
Conservation
PhyloP100: -0.836
Genes affected
MT-TS1 (HGNC:7497): (mitochondrially encoded tRNA serine 1 (UCN))
MT-CO1 (HGNC:7419): (mitochondrially encoded cytochrome c oxidase I) Contributes to cytochrome-c oxidase activity. Predicted to be involved in electron transport coupled proton transport and mitochondrial electron transport, cytochrome c to oxygen. Part of mitochondrial respiratory chain complex III and mitochondrial respiratory chain complex IV. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Mitotip and hmtvar scores support benign criterium.
BP6
?
Variant M-7476-C-T is Benign according to our data. Variant chrM-7476-C-T is described in ClinVar as [Benign]. Clinvar id is 42228.Status of the report is reviewed_by_expert_panel, 3 stars.
BA1
?
High frequency in mitomap database: 0.013200001
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TRNS1 | TRNS1.1 use as main transcript | n.39G>A | non_coding_transcript_exon_variant | 1/1 | |||
COX1 | COX1.1 use as main transcript | downstream_gene_variant | |||||
TRND | TRND.1 use as main transcript | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-TS1 | ENST00000387416.2 | n.39G>A | non_coding_transcript_exon_variant | 1/1 | |||||
MT-CO1 | ENST00000361624.2 | downstream_gene_variant | P1 | ||||||
MT-TD | ENST00000387419.1 | upstream_gene_variant |
Frequencies
GnomAD4 exome Cov.: 0
GnomAD4 exome
Cov.:
0
We have no GnomAD4 genomes data on this position. Probably position not covered by the project.
Mitomap GenBank
AF:
AC:
805
Gnomad homoplasmic
AF:
AC:
622
AN:
56432
Gnomad heteroplasmic
AF:
AC:
0
AN:
56432
Alfa
AF:
Hom.:
Mitomap
No disease associated.
ClinVar
Significance: Benign
Submissions summary: Benign:3
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 16, 2013 | m.7476C>T in MT-TS1: This variant is not expected to have clinical significance because it has been observed at equal frequencies in Caucasian individuals with hearing loss and in the general population (Houshmand 1994, Thomas 1996, Sternbe rg 1998, Li 2004, Konings 2008, mtDB-Human Mitochondrial Genome Database). - |
Mitochondrial disease Benign:1
Benign, reviewed by expert panel | curation | ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen | Jan 10, 2022 | The m.7476C>T variant in MT-TS1 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant is seen in 1.310% of individuals in the GenBank dataset (BA1), including in haplogroups J2a (99.7% of individuals) and J2b (98.85% of individuals). Furthermore, this variant is seen in the gnomAD dataset (v3.1.2) at an overall homoplasmic allele frequency of 1% including in haplogroup J at 20%. If an affected individual is not a member this haplogroup, further evaluation of the variant in that particular individual should be considered. The computational predictor MitoTIP suggests this variant does not impact the function of this tRNA with a score in the 20th percentile, as does HmtVar with a score of 0.1 (BP4). In summary, this variant meets criteria to be classified as benign. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BA1, BP4. - |
Juvenile myopathy, encephalopathy, lactic acidosis AND stroke Benign:1
Benign, criteria provided, single submitter | clinical testing | Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine | Jul 12, 2019 | The NC_012920.1:m.7476C>T variant in MT-TS1 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Mitotip
Benign
Hmtvar
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at