Variant chr5-150393369-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

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

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.3604-3C>T		splice_region_variant, intron_variant		ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2 link	c.3604-3C>T		splice_region_variant, intron_variant			NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.0846

AC:

12855

AN:

151864

Hom.:

629

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0642

AC:

16119

AN:

251238

Hom.:

622

AF XY:

0.0633

AC XY:

8595

AN XY:

135816

show subpopulations

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 SAS exome

AF:

0.0412

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.:

AF XY:

0.0717

AC XY:

52158

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.130

Gnomad4 AMR exome

AF:

0.0459

Gnomad4 ASJ exome

AF:

0.0351

Gnomad4 EAS exome

AF:

0.00892

Gnomad4 SAS exome

AF:

0.0404

Gnomad4 FIN exome

AF:

0.0662

Gnomad4 NFE exome

AF:

0.0779

Gnomad4 OTH exome

AF:

0.0713

GnomAD4 genome

AF:

0.0846

AC:

12861

AN:

151982

Hom.:

631

Cov.:

AF XY:

0.0830

AC XY:

6165

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.128

Gnomad4 AMR

AF:

0.0666

Gnomad4 ASJ

AF:

0.0337

Gnomad4 EAS

AF:

0.0140

Gnomad4 SAS

AF:

0.0367

Gnomad4 FIN

AF:

0.0662

Gnomad4 NFE

AF:

0.0764

Gnomad4 OTH

AF:

0.0887

Alfa

AF:

0.0787

Hom.:

591

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

LINK: link

Submissions by phenotype

not specified

Benign:2

Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	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. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Treacher Collins syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.94

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over