10-100989165-A-G
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PM1PM2PP2PP3_StrongPP5
The NM_021830.5(TWNK):c.955A>G(p.Lys319Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K319R) has been classified as Uncertain significance.
Frequency
Consequence
NM_021830.5 missense
Scores
Clinical Significance
Conservation
Publications
- progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
- mitochondrial DNA depletion syndrome 7 (hepatocerebral type)Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
- autosomal dominant progressive external ophthalmoplegiaInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- mitochondrial DNA depletion syndrome, hepatocerebrorenal formInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- Perrault syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 10 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD4 exome Cov.: 32
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 3 Pathogenic:1
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Sensory ataxic neuropathy, dysarthria, and ophthalmoparesis Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at