11-112086915-TTC-T
Variant names:
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_003002.4(SDHD):c.12_13delCT(p.Trp5GlufsTer63) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 32)
Consequence
SDHD
NM_003002.4 frameshift
NM_003002.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0730
Genes affected
SDHD (HGNC:10683): (succinate dehydrogenase complex subunit D) This gene encodes a member of complex II of the respiratory chain, which is responsible for the oxidation of succinate. The encoded protein is one of two integral membrane proteins anchoring the complex to the matrix side of the mitochondrial inner membrane. Mutations in this gene are associated with the formation of tumors, including hereditary paraganglioma. Transmission of disease occurs almost exclusively through the paternal allele, suggesting that this locus may be maternally imprinted. There are pseudogenes for this gene on chromosomes 1, 2, 3, 7, and 18. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]
TIMM8B (HGNC:11818): (translocase of inner mitochondrial membrane 8 homolog B) This gene encodes a member of a well-conserved family of proteins with similarity to yeast Tim mitochondrial import proteins. This gene is encoded by a nuclear gene and is transported into the intermembrane space of the mitochondrion. When formed into complexes, these proteins guide membrane-spanning proteins across the mitochondrial intermembrane space before they are added into the mitochondrial inner membrane. This gene is adjacent to succinate dehydrogenase, subunit D (SDHD), in which mutations have been found in affected members of families with hereditary paraganglioma.[provided by RefSeq, Aug 2009]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 47 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 11-112086915-TTC-T is Pathogenic according to our data. Variant chr11-112086915-TTC-T is described in ClinVar as [Likely_pathogenic]. Clinvar id is 806737.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| SDHD | ENST00000375549.8 | c.12_13delCT | p.Trp5GlufsTer63 | frameshift_variant | Exon 1 of 4 | 1 | NM_003002.4 | ENSP00000364699.3 | ||
| ENSG00000255292 | ENST00000532699.1 | n.12_13delCT | non_coding_transcript_exon_variant | Exon 1 of 6 | 3 | ENSP00000456434.1 | ||||
| TIMM8B | ENST00000504148.3 | c.-194_-193delGA | upstream_gene_variant | 1 | NM_012459.4 | ENSP00000422122.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Mar 01, 2017
CeGaT Center for Human Genetics Tuebingen
Significance: Likely pathogenic
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Computational scores
Source:
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Calibrated prediction
Score
Prediction
Splicing
Name
Calibrated prediction
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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