chr14-39154294-CCT-C
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_001079537.2(TRAPPC6B):c.268-2_268-1delAG variant causes a splice acceptor, intron change. The variant allele was found at a frequency of 0.0000174 in 1,605,614 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_001079537.2 splice_acceptor, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TRAPPC6B | NM_001079537.2 | c.268-2_268-1delAG | splice_acceptor_variant, intron_variant | Intron 3 of 5 | ENST00000330149.10 | NP_001073005.1 | ||
TRAPPC6B | NM_177452.4 | c.268-2457_268-2456delAG | intron_variant | Intron 3 of 4 | NP_803235.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000198 AC: 3AN: 151542Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 245928Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133598
GnomAD4 exome AF: 0.0000172 AC: 25AN: 1454072Hom.: 0 AF XY: 0.0000152 AC XY: 11AN XY: 723690
GnomAD4 genome AF: 0.0000198 AC: 3AN: 151542Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 73982
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with microcephaly, epilepsy, and brain atrophy Pathogenic:1
In-silico analysis tools suchas SpliceAI predict the variant to cause aberrant splicing. The variant c.268-2_268-1del was previouslyreported in four patients from the same family (Almousa et al. 2024). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at