chr12-6943663-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 10P and 1B. PVS1PM2BS1_Supporting
The NM_001301834.1(C12orf57):c.-16+1G>A variant causes a splice donor, intron 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
Consequence
NM_001301834.1 splice_donor, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
C12orf57 | ENST00000545581.5 | c.-16+1G>A | splice_donor_variant, intron_variant | Intron 1 of 3 | 3 | ENSP00000440602.1 | ||||
ENSG00000272173 | ENST00000607421.2 | n.968C>T | non_coding_transcript_exon_variant | Exon 1 of 1 | 6 | |||||
C12orf57 | ENST00000538392.1 | n.388+1G>A | splice_donor_variant, intron_variant | Intron 2 of 2 | 2 | |||||
C12orf57 | ENST00000542222.1 | n.230+1G>A | splice_donor_variant, intron_variant | Intron 1 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.000322 AC: 49AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000758 AC: 10AN: 132002Hom.: 0 AF XY: 0.0000835 AC XY: 6AN XY: 71898
GnomAD4 exome AF: 0.0000361 AC: 41AN: 1135690Hom.: 0 Cov.: 30 AF XY: 0.0000323 AC XY: 18AN XY: 557070
GnomAD4 genome AF: 0.000322 AC: 49AN: 152272Hom.: 0 Cov.: 32 AF XY: 0.000349 AC XY: 26AN XY: 74446
ClinVar
Submissions by phenotype
C12orf57-related disorder Uncertain:1
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
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at