10-100987903-CTG-C
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2
The NM_021830.5(TWNK):c.-304_-303del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 599,416 control chromosomes in the GnomAD database, including 7 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0039 ( 5 hom., cov: 32)
Exomes 𝑓: 0.00061 ( 2 hom. )
Consequence
TWNK
NM_021830.5 5_prime_UTR
NM_021830.5 5_prime_UTR
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.777
Genes affected
TWNK (HGNC:1160): (twinkle mtDNA helicase) This gene encodes a hexameric DNA helicase which unwinds short stretches of double-stranded DNA in the 5' to 3' direction and, along with mitochondrial single-stranded DNA binding protein and mtDNA polymerase gamma, is thought to play a key role in mtDNA replication. The protein localizes to the mitochondrial matrix and mitochondrial nucleoids. Mutations in this gene cause infantile onset spinocerebellar ataxia (IOSCA) and progressive external ophthalmoplegia (PEO) and are also associated with several mitochondrial depletion syndromes. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Aug 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -16 ACMG points.
BP6
Variant 10-100987903-CTG-C is Benign according to our data. Variant chr10-100987903-CTG-C is described in ClinVar as [Likely_benign]. Clinvar id is 298490.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00394 (600/152236) while in subpopulation AFR AF= 0.0139 (578/41518). AF 95% confidence interval is 0.013. There are 5 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TWNK | NM_021830.5 | c.-304_-303del | 5_prime_UTR_variant | 1/5 | ENST00000311916.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TWNK | ENST00000311916.8 | c.-304_-303del | 5_prime_UTR_variant | 1/5 | 1 | NM_021830.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00394 AC: 599AN: 152118Hom.: 5 Cov.: 32
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GnomAD4 exome AF: 0.000615 AC: 275AN: 447180Hom.: 2 AF XY: 0.000646 AC XY: 152AN XY: 235282
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GnomAD4 genome AF: 0.00394 AC: 600AN: 152236Hom.: 5 Cov.: 32 AF XY: 0.00369 AC XY: 275AN XY: 74434
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ClinVar
Significance: Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive cerebellar ataxia Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Ataxia Neuropathy Spectrum Disorders Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Mitochondrial DNA depletion syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Progressive external ophthalmoplegia with mitochondrial DNA deletions Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2021 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at