rs267606618
Positions:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000389680.2(MT-RNR1):n.448T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as drug response (★★★).
Frequency
Mitomap GenBank:
𝑓 0.0011 ( AC: 65 )
Consequence
MT-RNR1
ENST00000389680.2 non_coding_transcript_exon
ENST00000389680.2 non_coding_transcript_exon
Scores
Clinical Significance
SNHL
Conservation
PhyloP100: 2.56
Genes affected
MT-RNR1 (HGNC:7470): (mitochondrially encoded 12S RNA) Enables DNA binding activity and DNA-binding transcription factor binding activity. Involved in several processes, including osteoblast proliferation; regulation of carbohydrate utilization; and regulation of phosphate metabolic process. Located in extracellular space; mitochondrion; and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
?
High AC in GnomadMitoHomoplasmic at 21
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RNR1 | RNR1.1 use as main transcript | n.448T>C | non_coding_transcript_exon_variant | 1/1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MT-RNR1 | ENST00000389680.2 | n.448T>C | non_coding_transcript_exon_variant | 1/1 |
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:
65
Gnomad homoplasmic
AF:
AC:
21
AN:
56428
Gnomad heteroplasmic
AF:
AC:
1
AN:
56428
Mitomap
SNHL
ClinVar
Significance: drug response
Submissions summary: Pathogenic:3Uncertain:1Other:4
Revision: reviewed by expert panel
LINK: link
Submissions by phenotype
Auditory neuropathy Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 26, 2008 | - - |
Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 26, 2008 | - - |
Aminoglycoside-induced deafness Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 26, 2008 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 04, 2019 | The m.1095T>C variant has been reported in 24/2455 individuals with hearing loss, with and without aminoglycoside exposure (Thyagarajan 2000, Tessa 2001, Zhao 2004, Wang 2005, Li 2005, Dai 2006, Lu 2010, Shen 2001). In one Italian family with Parkinsonism, deafness and neuropathy, the variant segregated with hearing loss in at least two additional maternally related family members (Thyagaragan 2000), while in another family the variant segregated with nonsyndromic hearing loss in 4 family members (Tessa 2001), though alternate dominant inheritance cannot be ruled out. In addition, two functional studies show that the m.1095T>C variant impacts function (Thyagarajan 2000, Muderman 2012). Furthermore, a meta-analysis from several studies of mitochondrial hearing loss variants detected in hearing loss cohorts suggests that the m.1095T>C variant has a significant association with hearing loss when aminoglycoside exposure was assessed. However, this variant is reported in 0.12% (58/47,412) individuals in a broad population database (https://www.mitomap.org), and was a defining variant of the M11 haplogroup where it is present in 100% of individuals of that haplogroup (Tanaka 2004, Yao 2006). In summary, there is some evidence suggesting that the m.1095T>C variant may be associated with hearing loss, particularly with aminoglycoside exposure, however because of its frequency in the general population and the M11 haplogroup, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PS4_Moderate, PP1, PS3_Supporting, BS1_Supporting. - |
gentamicin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Jun 15, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Toxicity |
aminoglycoside antibacterials response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Jun 15, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Toxicity |
kanamycin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Jun 15, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Toxicity |
streptomycin response - Toxicity Other:1
drug response, reviewed by expert panel | curation | PharmGKB | Jun 15, 2021 | PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. Drug-variant association: Toxicity |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at