chr12-6943663-G-A
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000607421.2(ENSG00000272173):n.968C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000699 in 1,287,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).
Frequency
Genomes: 𝑓 0.00032 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 0 hom. )
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.249
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.72).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
C12orf57 | NM_001301834.1 | c.-16+1G>A | splice_donor_variant | ||||
C12orf57 | NM_001301836.2 | c.13+1G>A | splice_donor_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ENST00000607421.2 | n.968C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
C12orf57 | ENST00000545581.5 | c.-16+1G>A | splice_donor_variant | 3 | |||||
C12orf57 | ENST00000538392.1 | n.388+1G>A | splice_donor_variant, non_coding_transcript_variant | 2 | |||||
C12orf57 | ENST00000542222.1 | n.230+1G>A | splice_donor_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152154Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000758 AC: 10AN: 132002Hom.: 0 AF XY: 0.0000835 AC XY: 6AN XY: 71898
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GnomAD4 exome AF: 0.0000361 AC: 41AN: 1135690Hom.: 0 Cov.: 30 AF XY: 0.0000323 AC XY: 18AN XY: 557070
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GnomAD4 genome AF: 0.000322 AC: 49AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74446
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
C12orf57-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2023 | The C12orf57 c.13+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.15% of alleles in individuals of African descent in gnomAD. In a different transcript in which other splicing variants have been reported with epilepsy and neurodevelopmental disorder phenotypes (NM_138425), this variant is pre-coding (c.-459G>A). Taken together, while this variant could be pathogenic at this time we interpret its clinical significance as uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at