rs781925545
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PM4_Supporting
The ENST00000229281.6(C12orf57):βc.136_138delβ(p.Asp46del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000154 in 1,614,018 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (β β ).
Frequency
Genomes: π 0.000059 ( 0 hom., cov: 33)
Exomes π: 0.00016 ( 0 hom. )
Consequence
C12orf57
ENST00000229281.6 inframe_deletion
ENST00000229281.6 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.13
Genes affected
C12orf57 (HGNC:29521): (chromosome 12 open reading frame 57) This gene is ubiquitously expressed in human tissues. It is required for development of the human corpus callosum. Mutations in this gene are associated with Temtamy syndrome (TEMTYS). Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2014]
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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 ENST00000229281.6. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
C12orf57 | NM_138425.4 | c.136_138del | p.Asp46del | inframe_deletion | 2/3 | ENST00000229281.6 | NP_612434.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C12orf57 | ENST00000229281.6 | c.136_138del | p.Asp46del | inframe_deletion | 2/3 | 1 | NM_138425.4 | ENSP00000229281 | P1 | |
ENST00000607421.2 | n.72_74del | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000591 AC: 9AN: 152204Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000796 AC: 20AN: 251170Hom.: 0 AF XY: 0.0000883 AC XY: 12AN XY: 135858
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GnomAD4 exome AF: 0.000164 AC: 240AN: 1461814Hom.: 0 AF XY: 0.000154 AC XY: 112AN XY: 727206
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GnomAD4 genome AF: 0.0000591 AC: 9AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Jul 06, 2015 | - - |
Temtamy syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 27, 2023 | This variant, c.136_138del, results in the deletion of 1 amino acid(s) of the C12orf57 protein (p.Asp46del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781925545, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with C12orf57-related conditions. ClinVar contains an entry for this variant (Variation ID: 210546). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
Computational scores
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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