11-119018815-ATG-A
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_016146.6(TRAPPC4):c.23_24delTG(p.Val8GlyfsTer19) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000173 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Consequence
NM_016146.6 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251446Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1461872Hom.: 0 AF XY: 0.0000179 AC XY: 13AN XY: 727238
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74378
ClinVar
Submissions by phenotype
Neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy Pathogenic:1
This variant was detected in a proband (female) with severe intrauterine growth restriction, severe neonatal hypotrophy, growth retardation, severe intellectual disability, microcephaly, limb spasticity, together in trans with a well-known causative variant NM_016146.6(TRAPPC4):c.454+3A>G . The segregation analysis confirmed the maternal origin of the reported variant NM_016146.6(TRAPPC4):c.23_24del and paternal origin of the variant NM_016146.6(TRAPPC4):c.454+3A>G in proband. The pathogenic/likely pathogenic variants affecting the TRAPPC4 gene are well documented as a molecular cause of autosomal recessive "neurodevelopmental disorder with epilepsy, spasticity, and brain atrophy" (OMIM:618741) (PMID:32901138;32125366;31794024;34878169). To conclude, the variant is classified as likely pathogenic (ACMG PM2, PM3). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at