10-133557078-CTGTT-C
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_001143764.3(SYCE1):c.449_452del(p.Lys150ArgfsTer4) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,614,020 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000034 ( 0 hom. )
Consequence
SYCE1
NM_001143764.3 frameshift
NM_001143764.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.04
Genes affected
SYCE1 (HGNC:28852): (synaptonemal complex central element protein 1) This gene encodes a member of the synaptonemal complex, which links homologous chromosomes during prophase I of meiosis. The tripartite structure of the complex is highly conserved amongst metazoans. It consists of two lateral elements and a central region formed by transverse elements and a central element. The protein encoded by this gene localizes to the central element and is required for initiation and elongation of the synapsis. Allelic variants of this gene have been associated with premature ovarian failure and spermatogenic failure. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]
CYP2E1 (HGNC:2631): (cytochrome P450 family 2 subfamily E member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and is induced by ethanol, the diabetic state, and starvation. The enzyme metabolizes both endogenous substrates, such as ethanol, acetone, and acetal, as well as exogenous substrates including benzene, carbon tetrachloride, ethylene glycol, and nitrosamines which are premutagens found in cigarette smoke. Due to its many substrates, this enzyme may be involved in such varied processes as gluconeogenesis, hepatic cirrhosis, diabetes, and cancer. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-133557078-CTGTT-C is Pathogenic according to our data. Variant chr10-133557078-CTGTT-C is described in ClinVar as [Pathogenic]. Clinvar id is 1071187.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SYCE1 | NM_001143764.3 | c.449_452del | p.Lys150ArgfsTer4 | frameshift_variant | 7/13 | ENST00000343131.7 | |
SYCE1 | NM_001143763.2 | c.449_452del | p.Lys150ArgfsTer4 | frameshift_variant | 7/13 | ||
SYCE1 | NM_130784.4 | c.341_344del | p.Lys114ArgfsTer4 | frameshift_variant | 7/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SYCE1 | ENST00000343131.7 | c.449_452del | p.Lys150ArgfsTer4 | frameshift_variant | 7/13 | 1 | NM_001143764.3 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152192Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251490Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135918
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GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461828Hom.: 0 AF XY: 0.0000358 AC XY: 26AN XY: 727214
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 29, 2017 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SYCE1 are known to be pathogenic (PMID: 25062452, 25899990). This variant has not been reported in the literature in individuals with SYCE1-related disease. This variant is present in population databases (rs779142116, ExAC 0.003%). This sequence change creates a premature translational stop signal (p.Lys114Argfs*4) in the SYCE1 gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at