Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1PP5
The NM_001371623.1(TCOF1):c.376_378+15delAAGGTGAGTGGGACTGCC(p.Lys126del) variant causes a splice donor, conservative inframe deletion, splice region, intron change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Pathogenic (no stars).
TCOF1 (HGNC:11654): (treacle ribosome biogenesis factor 1) This gene encodes a nucleolar protein with a LIS1 homology domain. The protein is involved in ribosomal DNA gene transcription through its interaction with upstream binding factor (UBF). Mutations in this gene have been associated with Treacher Collins syndrome, a disorder which includes abnormal craniofacial development. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2008]
Our verdict: Likely_pathogenic. The variant received 9 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 5.4, offset of 25, new splice context is: aagGTgcct. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PP5
Variant 5-150367911-AGCCAAGGTGAGTGGGACT-A is Pathogenic according to our data. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr5-150367911-AGCCAAGGTGAGTGGGACT-A is described in CliVar as Pathogenic. Clinvar id is 3967.Status of the report is no_assertion_criteria_provided, 0 stars.