5-150392717-C-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001371623.1(TCOF1):c.3530C>G(p.Pro1177Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,613,690 control chromosomes in the GnomAD database, including 36,460 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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. P1177P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.16 ( 2581 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33879 hom. )

Consequence

TCOF1
NM_001371623.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.751

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053902566).

BP6

Variant 5-150392717-C-G is Benign according to our data. Variant chr5-150392717-C-G is described in ClinVar as [Benign]. Clinvar id is 130571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150392717-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.3530C>G	p.Pro1177Arg	missense_variant	Exon 22 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.3530C>G	p.Pro1177Arg	missense_variant	Exon 22 of 27		NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.160

AC:

24315

AN:

152094

Hom.:

2580

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.434

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0836

Gnomad FIN

AF:

0.249

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.161

GnomAD3 exomes

AF:

0.167

AC:

41803

AN:

249902

Hom.:

4530

AF XY:

0.170

AC XY:

23048

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.0362

Gnomad AMR exome

AF:

0.100

Gnomad ASJ exome

AF:

0.224

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.0865

Gnomad FIN exome

AF:

0.242

Gnomad NFE exome

AF:

0.235

Gnomad OTH exome

AF:

0.196

GnomAD4 exome

AF:

0.206

AC:

301223

AN:

1461478

Hom.:

33879

Cov.:

AF XY:

0.204

AC XY:

148233

AN XY:

727038

show subpopulations

Gnomad4 AFR exome

AF:

0.0327

Gnomad4 AMR exome

AF:

0.106

Gnomad4 ASJ exome

AF:

0.224

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.0918

Gnomad4 FIN exome

AF:

0.240

Gnomad4 NFE exome

AF:

0.231

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.160

AC:

24316

AN:

152212

Hom.:

2581

Cov.:

AF XY:

0.156

AC XY:

11621

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0409

Gnomad4 AMR

AF:

0.143

Gnomad4 ASJ

AF:

0.218

Gnomad4 EAS

AF:

0.000968

Gnomad4 SAS

AF:

0.0843

Gnomad4 FIN

AF:

0.249

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.160

Alfa

AF:

0.200

Hom.:

2517

Bravo

AF:

0.149

TwinsUK

AF:

0.243

AC:

901

ALSPAC

AF:

0.226

AC:

872

ESP6500AA

AF:

0.0456

AC:

201

ESP6500EA

AF:

0.235

AC:

2018

ExAC

AF:

0.169

AC:

20570

EpiCase

AF:

0.224

EpiControl

AF:

0.229

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

Feb 03, 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

0.091

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.48

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

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.54

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

MetaRNN

Benign

0.0054

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

.;L;.;.;.;.;.;.;L;.

PrimateAI

Benign

0.31

PROVEAN

Pathogenic

-4.8

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

REVEL

Benign

0.11

Sift

Benign

0.046

.;.;D;T;.;.;D;D;T;D

Sift4G

Uncertain

0.029

.;D;T;D;.;.;T;T;D;T

Polyphen

1.0, 0.95, 0.97

.;D;P;P;.;.;D;D;D;.

Vest4

0.16, 0.34, 0.34, 0.44, 0.40

MPC

0.27

ClinPred

0.037

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.086

gMVP

0.074

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

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