3-196707649-CCTT-C
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The NM_032898.5(CEP19):βc.391_393delβ(p.Lys131del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.0000274 in 1,461,802 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β ).
Frequency
Genomes: π 0.000046 ( 0 hom., cov: 32)
Exomes π: 0.000027 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CEP19
NM_032898.5 inframe_deletion
NM_032898.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 4.56
Genes affected
CEP19 (HGNC:28209): (centrosomal protein 19) The protein encoded by this gene localizes to centrosomes and primary cilia and co-localizes with a marker for the mother centriole. This gene resides in a region of human chromosome 3 that is linked to morbid obesity. A homozygous knockout of the orthologous gene in mouse resulted in mice with morbid obesity, hyperphagy, glucose intolerance, and insulin resistance. Mutations in this gene cause morbid obesity and spermatogenic failure (MOSPGF). This gene has a pseudogene on human chromosome 2. [provided by RefSeq, Apr 2014]
PIGX (HGNC:26046): (phosphatidylinositol glycan anchor biosynthesis class X) This gene encodes a type I transmembrane protein in the endoplasmic reticulum (ER). The protein is an essential component of glycosylphosphatidylinositol-mannosyltransferase I, which transfers the first of the four mannoses in the GPI-anchor precursors during GPI-anchor biosynthesis. Studies in rat indicate that the protein is translated from a non-AUG translation initiation site. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
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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
Nonframeshift variant in NON repetitive region in NM_032898.5. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| CEP19 | NM_032898.5 | c.391_393del | p.Lys131del | inframe_deletion | 3/3 | ENST00000409690.5 | NP_116287.3 | |
| CEP19 | NM_001379468.1 | c.286_288del | p.Lys96del | inframe_deletion | 2/2 | NP_001366397.1 | ||
| CEP19 | NM_001379469.1 | c.391_393del | p.Lys131del | inframe_deletion | 3/3 | NP_001366398.1 | ||
| CEP19 | NM_001379470.1 | c.391_393del | p.Lys131del | inframe_deletion | 3/3 | NP_001366399.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| CEP19 | ENST00000409690.5 | c.391_393del | p.Lys131del | inframe_deletion | 3/3 | 1 | NM_032898.5 | ENSP00000387209 | P1 | |
| CEP19 | ENST00000399942.4 | c.286_288del | p.Lys96del | inframe_deletion | 2/2 | 5 | ENSP00000382823 | |||
| PIGX | ENST00000426755.5 | c.-11-9200_-11-9198del | intron_variant | 3 | ENSP00000409073 |
Frequencies
GnomAD3 genomes 0.00 AC: 7AN: 152086Hom.: 0 Cov.: 32 FAILED QC
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GnomAD3 exomes AF: 0.0000441 AC: 11AN: 249458Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135370
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GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461802Hom.: 0 AF XY: 0.0000248 AC XY: 18AN XY: 727216
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GnomAD4 genome 0.0000460 AC: 7AN: 152086Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74292
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
| Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 22, 2022 | This variant, c.403_405del, results in the deletion of 1 amino acid(s) of the CEP19 protein (p.Lys135del), but otherwise preserves the integrity of the reading frame. 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. This variant has not been reported in the literature in individuals affected with CEP19-related conditions. This variant is present in population databases (rs750813457, gnomAD 0.03%). - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at