11-68036607-C-T
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_002496.4(NDUFS8):c.*14C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,612,862 control chromosomes in the GnomAD database, including 25,115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.18 ( 2704 hom., cov: 33)
Exomes 𝑓: 0.17 ( 22411 hom. )
Consequence
NDUFS8
NM_002496.4 3_prime_UTR
NM_002496.4 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.530
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.77).
BP6
Variant 11-68036607-C-T is Benign according to our data. Variant chr11-68036607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 305774.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.237 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
NDUFS8 | NM_002496.4 | c.*14C>T | 3_prime_UTR_variant | 7/7 | ENST00000313468.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
NDUFS8 | ENST00000313468.10 | c.*14C>T | 3_prime_UTR_variant | 7/7 | 1 | NM_002496.4 | P1 | ||
NDUFS8 | ENST00000528492.1 | c.*14C>T | 3_prime_UTR_variant | 3/3 | 1 | ||||
NDUFS8 | ENST00000531282.1 | n.499C>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
NDUFS8 | ENST00000524810.5 | c.*298C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/4 | 2 |
Frequencies
GnomAD3 genomes AF: 0.182 AC: 27649AN: 152128Hom.: 2702 Cov.: 33
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GnomAD3 exomes AF: 0.149 AC: 37255AN: 249630Hom.: 3116 AF XY: 0.148 AC XY: 20000AN XY: 135328
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GnomAD4 exome AF: 0.171 AC: 249402AN: 1460616Hom.: 22411 Cov.: 33 AF XY: 0.169 AC XY: 122963AN XY: 726588
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GnomAD4 genome AF: 0.182 AC: 27662AN: 152246Hom.: 2704 Cov.: 33 AF XY: 0.175 AC XY: 12998AN XY: 74448
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Mitochondrial complex I deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Mitochondrial complex I deficiency, nuclear type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Leigh syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 03, 2015 | - - |
Osteopetrosis Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
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DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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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