5-150372182-TAGTGAGGAGGGATCTGAA-TAGTGAGGAGGGATCTGAAAGTGAGGAGGGATCTGAA

Variant names:

• chr5-150372182-T-TAGTGAGGAGGGATCTGAA
• rs528897827
• NM_001371623.1:c.827_844dupGATCTGAAAGTGAGGAGG

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_001371623.1(TCOF1):​c.827_844dupGATCTGAAAGTGAGGAGG​(p.Gly276_Glu281dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. 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 INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: TCOF1 NM_001371623.1 disruptive_inframe_insertion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.94
• 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, PanelApp Australia
• Treacher-Collins syndrome

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001371623.1.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371623.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	NM_001371623.1	MANE Select	c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 27	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 27	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 26	NP_001128716.1	Q13428-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 27	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 26	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000394269.7	TSL:1	c.827_844dupGATCTGAAAGTGAGGAGG	p.Gly276_Glu281dup	disruptive_inframe_insertion	Exon 7 of 18	ENSP00000377811.3	Q13428-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Treacher Collins syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.9

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs528897827;

hg19: chr5-149751745;