5-150375777-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001371623.1(TCOF1):c.1761G>T(p.Gly587Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0754 in 1,614,172 control chromosomes in the GnomAD database, including 5,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.092 ( 785 hom., cov: 34)

Exomes 𝑓: 0.074 ( 4304 hom. )

Consequence

TCOF1
NM_001371623.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.12

Publications

12 publications found

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 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

TCOF1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 5-150375777-G-T is Benign according to our data. Variant chr5-150375777-G-T is described in ClinVar as [Benign]. Clinvar id is 130564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.12 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.149 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.1761G>T	p.Gly587Gly	synonymous_variant	Exon 12 of 27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2 link	c.1761G>T	p.Gly587Gly	synonymous_variant	Exon 12 of 27		NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.0917

AC:

13948

AN:

152170

Hom.:

782

Cov.:

show subpopulations

Gnomad AFR

AF:

0.152

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0678

Gnomad ASJ

AF:

0.0337

Gnomad EAS

AF:

0.0152

Gnomad SAS

AF:

0.0443

Gnomad FIN

AF:

0.0660

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0764

Gnomad OTH

AF:

0.0926

GnomAD2 exomes

AF:

0.0668

AC:

16780

AN:

251354

AF XY:

0.0657

show subpopulations

Gnomad AFR exome

AF:

0.155

Gnomad AMR exome

AF:

0.0455

Gnomad ASJ exome

AF:

0.0363

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0673

Gnomad NFE exome

AF:

0.0771

Gnomad OTH exome

AF:

0.0661

GnomAD4 exome

AF:

0.0737

AC:

107761

AN:

1461884

Hom.:

4304

Cov.:

AF XY:

0.0729

AC XY:

53022

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.156

AC:

5230

AN:

33480

American (AMR)

AF:

0.0469

AC:

2099

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

918

AN:

26136

East Asian (EAS)

AF:

0.00917

AC:

364

AN:

39700

South Asian (SAS)

AF:

0.0458

AC:

3950

AN:

86256

European-Finnish (FIN)

AF:

0.0662

AC:

3535

AN:

53418

Middle Eastern (MID)

AF:

0.0730

AC:

421

AN:

5768

European-Non Finnish (NFE)

AF:

0.0780

AC:

86761

AN:

1112008

Other (OTH)

AF:

0.0742

AC:

4483

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

6733

13466

20198

26931

33664

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0917

AC:

13968

AN:

152288

Hom.:

785

Cov.:

AF XY:

0.0899

AC XY:

6691

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.152

AC:

6335

AN:

41554

American (AMR)

AF:

0.0677

AC:

1035

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0337

AC:

117

AN:

3470

East Asian (EAS)

AF:

0.0153

AC:

AN:

5176

South Asian (SAS)

AF:

0.0435

AC:

210

AN:

4832

European-Finnish (FIN)

AF:

0.0660

AC:

701

AN:

10616

Middle Eastern (MID)

AF:

0.0748

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0764

AC:

5197

AN:

68020

Other (OTH)

AF:

0.0912

AC:

193

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

596

1192

1788

2384

2980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0856

Hom.:

299

Bravo

AF:

0.0947

Asia WGS

AF:

0.0560

AC:

194

AN:

3478

EpiCase

AF:

0.0740

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

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.26

(source)

DANN

Benign

0.36

PhyloP100

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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5-150375777-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over