rs267606618
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP5_StrongBS2
Variant has been reported in ClinVar as drug response (★★★).
Frequency
Consequence
non_coding_transcript_exon
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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RNR1 | unassigned_transcript_4785 | n.448T>C | non_coding_transcript_exon_variant | Exon 1 of 1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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Frequencies
GnomAD4 exome Cov.: 0
Mitomap
ClinVar
Submissions by phenotype
Auditory neuropathy Pathogenic:1
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Mitochondrial non-syndromic sensorineural hearing loss Pathogenic:1
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not provided Pathogenic:1
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Aminoglycoside-induced deafness Pathogenic:1
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not specified Uncertain:1
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
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
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
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
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:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at