20-13785097-T-A
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_024120.5(NDUFAF5):c.29T>A(p.Leu10Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. L10L) has been classified as Likely benign.
Frequency
Consequence
NM_024120.5 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFAF5 | NM_024120.5 | c.29T>A | p.Leu10Ter | stop_gained | 1/11 | ENST00000378106.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFAF5 | ENST00000378106.10 | c.29T>A | p.Leu10Ter | stop_gained | 1/11 | 1 | NM_024120.5 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247458Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134692
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460880Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726788
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Mitochondrial complex 1 deficiency, nuclear type 16 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 09, 2023 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with mitochondrial complex I deficiency (PMID: 26275793). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (no rsID available, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Leu10*) in the NDUFAF5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NDUFAF5 are known to be pathogenic (PMID: 26275793, 30473481, 32918965). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at