5-150396792-G-C

Position:

chr5-150396792-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001371623.1(TCOF1):c.4295G>C(p.Gly1432Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0214 in 1,610,616 control chromosomes in the GnomAD database, including 444 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.018 ( 43 hom., cov: 31)

Exomes 𝑓: 0.022 ( 401 hom. )

Consequence

TCOF1
NM_001371623.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.836

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=0.0030030906).

BP6

Variant 5-150396792-G-C is Benign according to our data. Variant chr5-150396792-G-C is described in ClinVar as [Benign]. Clinvar id is 130575.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr5-150396792-G-C is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0178 (2711/152132) while in subpopulation AMR AF= 0.0294 (449/15278). AF 95% confidence interval is 0.0271. There are 43 homozygotes in gnomad4. There are 1351 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2711 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TCOF1	NM_001371623.1 linkuse as main transcript	c.4295G>C	p.Gly1432Ala	missense_variant	24/27	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.4295G>C	p.Gly1432Ala	missense_variant	24/27		NM_001371623.1	ENSP00000493815	P3	Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2710

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00420

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.0294

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00911

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0248

Gnomad OTH

AF:

0.0239

GnomAD3 exomes

AF:

0.0185

AC:

4478

AN:

242024

Hom.:

AF XY:

0.0189

AC XY:

2489

AN XY:

131640

show subpopulations

Gnomad AFR exome

AF:

0.00364

Gnomad AMR exome

AF:

0.0201

Gnomad ASJ exome

AF:

0.0328

Gnomad EAS exome

AF:

0.0000554

Gnomad SAS exome

AF:

0.00743

Gnomad FIN exome

AF:

0.0127

Gnomad NFE exome

AF:

0.0258

Gnomad OTH exome

AF:

0.0217

GnomAD4 exome

AF:

0.0217

AC:

31697

AN:

1458484

Hom.:

401

Cov.:

AF XY:

0.0216

AC XY:

15635

AN XY:

725228

show subpopulations

Gnomad4 AFR exome

AF:

0.00409

Gnomad4 AMR exome

AF:

0.0213

Gnomad4 ASJ exome

AF:

0.0334

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00830

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0243

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0178

AC:

2711

AN:

152132

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

1351

AN XY:

74378

show subpopulations

Gnomad4 AFR

AF:

0.00417

Gnomad4 AMR

AF:

0.0294

Gnomad4 ASJ

AF:

0.0323

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00911

Gnomad4 FIN

AF:

0.0113

Gnomad4 NFE

AF:

0.0248

Gnomad4 OTH

AF:

0.0237

Alfa

AF:

0.0242

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.0229

AC:

ALSPAC

AF:

0.0257

AC:

ESP6500AA

AF:

0.00386

AC:

ESP6500EA

AF:

0.0212

AC:

182

ExAC

AF:

0.0175

AC:

2120

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	curation	SIB Swiss Institute of Bioinformatics	May 31, 2018	This variant is interpreted as a Benign - Stand Alone. The following ACMG Tag(s) were applied: BA1 => Allele frequency is >3% in Exome Aggregation Consortium (European non-Finnish population). -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Nov 14, 2018	- -

Treacher Collins syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.51

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

Eigen

Benign

-0.30

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.18

LIST_S2

Uncertain

0.88

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

MetaRNN

Benign

0.0030

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

MetaSVM

Uncertain

-0.27

MutationAssessor

Benign

1.8

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

MutationTaster

Benign

1.0

N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Uncertain

-2.8

.;D;D;D;.;.;D;D;D;D;N

REVEL

Benign

0.19

Sift

Benign

0.042

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

Sift4G

Uncertain

0.047

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

Polyphen

0.41, 0.93

.;B;P;P;.;.;P;P;B;.;.

Vest4

0.098, 0.19, 0.19, 0.29, 0.28

MPC

0.41

ClinPred

0.018

GERP RS

0.69

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.2

Varity_R

0.14

gMVP

0.0024

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