5-150379638-C-T

Position:

chr5-150379638-C-T

Variant summary

Our verdict is Benign. Variant got -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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as 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

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:

TCOF1 (HGNC:):

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=0.0028220415).

BP6

Variant 5-150379638-C-T is Benign according to our data. Variant chr5-150379638-C-T is described in ClinVar as [Benign]. Clinvar id is 130570.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150379638-C-T is described in Lovd as [Likely_benign].

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/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript	c.2765C>T	p.Ser922Leu	missense_variant	17/27	ENST00000643257.2	NP_001358552.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TCOF1	ENST00000643257.2 linkuse as main transcript	c.2765C>T	p.Ser922Leu	missense_variant	17/27		NM_001371623.1	ENSP00000493815.1		Q13428-3

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

GnomAD3 exomes

AF:

0.00685

AC:

1720

AN:

251162

Hom.:

AF XY:

0.00550

AC XY:

747

AN XY:

135772

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 SAS exome

AF:

0.00160

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

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.00546

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00154

Gnomad4 FIN exome

AF:

0.00317

Gnomad4 NFE exome

AF:

0.00144

Gnomad4 OTH exome

AF:

0.00632

GnomAD4 genome

AF:

0.0209

AC:

3176

AN:

152292

Hom.:

100

Cov.:

AF XY:

0.0197

AC XY:

1467

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0685

Gnomad4 AMR

AF:

0.00888

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00424

Gnomad4 NFE

AF:

0.00162

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.00385

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 25, 2016	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. -
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	-	- -

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

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.43

CADD

Benign

2.2

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;.

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

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