rs3115545
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_002496.4(NDUFS8):c.199+15T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000267 in 1,613,686 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 Likely benign (★★).
Frequency
Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
NDUFS8
NM_002496.4 intron
NM_002496.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -2.71
Genes affected
NDUFS8 (HGNC:7715): (NADH:ubiquinone oxidoreductase core subunit S8) This gene encodes a subunit of mitochondrial NADH:ubiquinone oxidoreductase, or Complex I, a multimeric enzyme of the respiratory chain responsible for NADH oxidation, ubiquinone reduction, and the ejection of protons from mitochondria. The encoded protein is involved in the binding of two of the six to eight iron-sulfur clusters of Complex I and, as such, is required in the electron transfer process. Mutations in this gene have been associated with Leigh syndrome. [provided by RefSeq, Mar 2010]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.99).
BP6
?
Variant 11-68033027-T-A is Benign according to our data. Variant chr11-68033027-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 380968.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 = 0.00148 (226/152308) while in subpopulation AFR AF= 0.00527 (219/41552). AF 95% confidence interval is 0.0047. There are 0 homozygotes in gnomad4. There are 104 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS8 | NM_002496.4 | c.199+15T>A | intron_variant | ENST00000313468.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS8 | ENST00000313468.10 | c.199+15T>A | intron_variant | 1 | NM_002496.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00147 AC: 224AN: 152190Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000319 AC: 80AN: 250596Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135696
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GnomAD4 exome AF: 0.000140 AC: 205AN: 1461378Hom.: 0 Cov.: 63 AF XY: 0.000118 AC XY: 86AN XY: 727010
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GnomAD4 genome ? AF: 0.00148 AC: 226AN: 152308Hom.: 0 Cov.: 33 AF XY: 0.00140 AC XY: 104AN XY: 74472
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 11, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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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