chr5-150367911-AGCCAAGGTGAGTGGGACT-A

Variant names:

• chr5-150367911-AGCCAAGGTGAGTGGGACT-A
• rs587776584
• NM_001371623.1:c.376_378+15delAAGGTGAGTGGGACTGCC

Variant summary

Our verdict is Likely pathogenic. The variant received 9 ACMG points: 9P and 0B. PVS1 PP5

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).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TCOF1 NM_001371623.1 splice_donor, conservative_inframe_deletion, splice_region, intron
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 3.72
• Publications: 0 publications found

Genes affected

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]

TCOF1 Gene-Disease associations (from GenCC):

• Treacher Collins syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1	c.376_378+15delAAGGTGAGTGGGACTGCC	p.Lys126del	splice_donor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant	Exon 4 of 27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2	c.376_378+15delAAGGTGAGTGGGACTGCC	p.Lys126del	splice_donor_variant, conservative_inframe_deletion, splice_region_variant, intron_variant	Exon 4 of 27		NM_001371623.1	ENSP00000493815.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Treacher Collins syndrome 1 Pathogenic:1

Dec 01, 2003

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.7
Mutation Taster		=3/197	disease causing (ClinVar)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs587776584; hg19: chr5-149747474;