5-150393369-C-T

Variant names:

• chr5-150393369-C-T
• rs11743855
• NM_001371623.1:c.3604-3C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_001371623.1(TCOF1):​c.3604-3C>T variant causes a splice region, intron change. The variant allele was found at a frequency of 0.0737 in 1,613,700 control chromosomes in the GnomAD database, including 4,779 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.085 (631 hom., cov: 32)
  • Exomes 𝑓: 0.073 (4148 hom.)
• Consequence: TCOF1 NM_001371623.1 splice_region, intron
• Scores: Splicing: ADA: 0.4293
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.10
• Publications: 12 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: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 5-150393369-C-T is Benign according to our data. Variant chr5-150393369-C-T is described in ClinVar as Benign. ClinVar VariationId is 130572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.125 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	NM_001371623.1	MANE Select	c.3604-3C>T		splice_region intron	N/A	NP_001358552.1
	TCOF1	NM_001135243.2		c.3601-3C>T		splice_region intron	N/A	NP_001128715.1
	TCOF1	NM_001135244.2		c.3490-3C>T		splice_region intron	N/A	NP_001128716.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TCOF1	ENST00000643257.2	MANE Select	c.3604-3C>T		splice_region intron	N/A	ENSP00000493815.1
	TCOF1	ENST00000504761.6	TSL:1	c.3601-3C>T		splice_region intron	N/A	ENSP00000421655.2
	TCOF1	ENST00000323668.11	TSL:1	c.3370-3C>T		splice_region intron	N/A	ENSP00000325223.6

Frequencies

GnomAD3 genomes AF: 0.0846 AC: 12855 AN: 151864 Hom.: 629 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.0866

Gnomad AMR AF: 0.0667

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.0140

Gnomad SAS AF: 0.0375

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0764

Gnomad OTH AF: 0.0901

GnomAD2 exomes AF: 0.0642 AC: 16119 AN: 251238 AF XY: 0.0633

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.0445

Gnomad ASJ exome AF: 0.0363

Gnomad EAS exome AF: 0.0133

Gnomad FIN exome AF: 0.0671

Gnomad NFE exome AF: 0.0770

Gnomad OTH exome AF: 0.0644

GnomAD4 exome AF: 0.0726 AC: 106052 AN: 1461718 Hom.: 4148 Cov.: 31 AF XY: 0.0717 AC XY: 52158 AN XY: 727180

African (AFR) AF: 0.130 AC: 4339 AN: 33480

American (AMR) AF: 0.0459 AC: 2054 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0351 AC: 918 AN: 26134

East Asian (EAS) AF: 0.00892 AC: 354 AN: 39698

South Asian (SAS) AF: 0.0404 AC: 3488 AN: 86252

European-Finnish (FIN) AF: 0.0662 AC: 3534 AN: 53408

Middle Eastern (MID) AF: 0.0698 AC: 402 AN: 5760

European-Non Finnish (NFE) AF: 0.0779 AC: 86658 AN: 1111884

Other (OTH) AF: 0.0713 AC: 4305 AN: 60380

GnomAD4 genome AF: 0.0846 AC: 12861 AN: 151982 Hom.: 631 Cov.: 32 AF XY: 0.0830 AC XY: 6165 AN XY: 74286

African (AFR) AF: 0.128 AC: 5299 AN: 41412

American (AMR) AF: 0.0666 AC: 1017 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0337 AC: 117 AN: 3470

East Asian (EAS) AF: 0.0140 AC: 72 AN: 5148

South Asian (SAS) AF: 0.0367 AC: 177 AN: 4822

European-Finnish (FIN) AF: 0.0662 AC: 700 AN: 10580

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0764 AC: 5192 AN: 67966

Other (OTH) AF: 0.0887 AC: 187 AN: 2108

Alfa AF: 0.0792 Hom.: 841

Bravo AF: 0.0871

Asia WGS AF: 0.0380 AC: 131 AN: 3478

EpiCase AF: 0.0739

EpiControl AF: 0.0762

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.

not provided Benign:1

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Treacher Collins syndrome 1 Benign:1

Jan 30, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.94
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.43
dbscSNV1_RF	Benign	0.28
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11743855; hg19: chr5-149772932;