rs753367800
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_152416.4(NDUFAF6):βc.557_559delβ(p.Leu186_Tyr187delinsHis) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000112 in 1,612,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.0000066 ( 0 hom., cov: 32)
Exomes π: 0.000012 ( 0 hom. )
Consequence
NDUFAF6
NM_152416.4 inframe_deletion
NM_152416.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.00
Genes affected
NDUFAF6 (HGNC:28625): (NADH:ubiquinone oxidoreductase complex assembly factor 6) This gene encodes a protein that localizes to mitochondria and contains a predicted phytoene synthase domain. The encoded protein plays an important role in the assembly of complex I (NADH-ubiquinone oxidoreductase) of the mitochondrial respiratory chain through regulation of subunit ND1 biogenesis. Mutations in this gene are associated with complex I enzymatic deficiency. [provided by RefSeq, Nov 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PM4
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Nonframeshift variant in NON repetitive region in NM_152416.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFAF6 | NM_152416.4 | c.557_559del | p.Leu186_Tyr187delinsHis | inframe_deletion | 5/9 | ENST00000396124.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFAF6 | ENST00000396124.9 | c.557_559del | p.Leu186_Tyr187delinsHis | inframe_deletion | 5/9 | 2 | NM_152416.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000281 AC: 7AN: 249274Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135252
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460488Hom.: 0 AF XY: 0.0000165 AC XY: 12AN XY: 726650
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental regression Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Centre for Mendelian Genomics, University Medical Centre Ljubljana | Jan 01, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 29, 2021 | This variant is present in population databases (rs753367800, ExAC 0.003%). This variant, c.557_559del, is a complex sequence change that results in the deletion of 2 and insertion of 1 amino acid(s) in the NDUFAF6 protein (p.Leu186_Tyr187delinsHis). This variant has not been reported in the literature in individuals affected with NDUFAF6-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 523559). - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at