5-150379638-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001371623.1(TCOF1):c.2765C>T(p.Ser922Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00503 in 1,614,150 control chromosomes in the GnomAD database, including 208 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S922S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.021 ( 100 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 108 hom. )

Consequence

TCOF1
NM_001371623.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.491

Publications

6 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028220415).

BP6

Variant 5-150379638-C-T is Benign according to our data. Variant chr5-150379638-C-T is described in ClinVar as Benign. ClinVar VariationId is 130570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0664 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.2765C>T	p.Ser922Leu	missense_variant	Exon 17 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.2765C>T	p.Ser922Leu	missense_variant	Exon 17 of 27		NM_001371623.1	ENSP00000493815.1

Frequencies

GnomAD3 genomes

AF:

0.0209

AC:

3179

AN:

152174

Hom.:

102

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0688

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00890

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00424

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00162

Gnomad OTH

AF:

0.0148

GnomAD2 exomes

AF:

0.00685

AC:

1720

AN:

251162

AF XY:

0.00550

show subpopulations

Gnomad AFR exome

AF:

0.0705

Gnomad AMR exome

AF:

0.00520

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00305

Gnomad NFE exome

AF:

0.00232

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00338

AC:

4939

AN:

1461858

Hom.:

108

Cov.:

AF XY:

0.00308

AC XY:

2237

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.0713

AC:

2387

AN:

33480

American (AMR)

AF:

0.00546

AC:

244

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00154

AC:

133

AN:

86258

European-Finnish (FIN)

AF:

0.00317

AC:

169

AN:

53384

Middle Eastern (MID)

AF:

0.00347

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00144

AC:

1604

AN:

1112012

Other (OTH)

AF:

0.00632

AC:

382

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

357

714

1072

1429

1786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0209

AC:

3176

AN:

152292

Hom.:

100

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74462

show subpopulations

African (AFR)

AF:

0.0685

AC:

2847

AN:

41552

American (AMR)

AF:

0.00888

AC:

136

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00424

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00162

AC:

110

AN:

68018

Other (OTH)

AF:

0.0147

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

145

290

435

580

725

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

160

200

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00781

Hom.:

Bravo

AF:

0.0235

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0638

AC:

281

ESP6500EA

AF:

0.00128

AC:

ExAC

AF:

0.00872

AC:

1059

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.00131

EpiControl

AF:

0.00154

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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. -

Jan 25, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Treacher Collins syndrome 1

Benign:1

Jan 28, 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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.2

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.20

.;T;.;.;.;.;.;.;.;.;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.66

T;T;T;T;.;T;T;T;T;T;.;T

MetaRNN

Benign

0.0028

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

.;N;.;.;N;.;N;N;N;N;N;.

PhyloP100

-0.49

PrimateAI

Benign

0.30

PROVEAN

Benign

-2.2

.;N;N;N;.;.;.;N;N;N;N;N

REVEL

Benign

0.080

Sift

Uncertain

0.017

.;D;D;D;.;.;.;D;D;D;D;D

Sift4G

Benign

0.34

.;T;T;T;.;.;.;T;T;T;T;T

Polyphen

0.0010

.;B;B;B;.;.;.;B;B;B;B;.

Vest4

0.063, 0.051, 0.048, 0.054, 0.045, 0.069

MVP

0.12

MPC

0.069

ClinPred

0.0037

GERP RS

0.39

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

Varity_R

0.050

gMVP

0.072

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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