rs151344581

Variant names:

• chr5-150398379-AAAGAAG-A
• rs151344581
• NM_001371623.1:c.4377_4382delGAAGAA

Your query was ambiguous. Multiple possible variants found:

• chr5-150398379-AAAGAAG-A
• chr5-150398379-AAAGAAG-AAAG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001371623.1(TCOF1):​c.4377_4382delGAAGAA​(p.Lys1460_Lys1461del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000479 in 1,461,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: TCOF1 NM_001371623.1 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.90
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
• Treacher-Collins syndrome

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

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001371623.1
• BS2: High AC in GnomAdExome4 at 7 AD gene.

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.4377_4382delGAAGAA	p.Lys1460_Lys1461del	disruptive_inframe_deletion	Exon 25 of 27	NP_001358552.1	Q13428-3
	TCOF1	NM_001135243.2		c.4374_4379delGAAGAA	p.Lys1459_Lys1460del	disruptive_inframe_deletion	Exon 25 of 27	NP_001128715.1	Q13428-1
	TCOF1	NM_001135244.2		c.4263_4268delGAAGAA	p.Lys1422_Lys1423del	disruptive_inframe_deletion	Exon 24 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.4377_4382delGAAGAA	p.Lys1460_Lys1461del	disruptive_inframe_deletion	Exon 25 of 27	ENSP00000493815.1	Q13428-3
	TCOF1	ENST00000504761.6	TSL:1	c.4374_4379delGAAGAA	p.Lys1459_Lys1460del	disruptive_inframe_deletion	Exon 25 of 26	ENSP00000421655.2	Q13428-1
	TCOF1	ENST00000323668.11	TSL:1	c.4143_4148delGAAGAA	p.Lys1382_Lys1383del	disruptive_inframe_deletion	Exon 24 of 26	ENSP00000325223.6	Q13428-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 248098 AF XY: 0.0000149

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000271

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461322 Hom.: 0 AF XY: 0.00000550 AC XY: 4 AN XY: 727000

African (AFR) AF: 0.00 AC: 0 AN: 33336

American (AMR) AF: 0.00 AC: 0 AN: 44566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86186

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53412

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000630 AC: 7 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60346

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000364 Hom.: 0

Bravo AF: 0.00000756

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		3.9
Mutation Taster		=82/118	disease causing

Splicing

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

Other links and lift over

dbSNP: rs151344581; hg19: chr5-149777942;