rs574569798

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBS1BS2

The NM_001371623.1(TCOF1):c.4332_4334delGAA(p.Lys1445del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00343 in 1,605,566 control chromosomes in the GnomAD database, including 13 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 30)

Exomes 𝑓: 0.0035 ( 12 hom. )

Consequence

TCOF1
NM_001371623.1 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 4.69

Publications

3 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 -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001371623.1. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 5-150396821-GAGA-G is Benign according to our data. Variant chr5-150396821-GAGA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 352236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00322 (490/152156) while in subpopulation NFE AF = 0.0044 (299/68000). AF 95% confidence interval is 0.00399. There are 1 homozygotes in GnomAd4. There are 270 alleles in the male GnomAd4 subpopulation. Median coverage is 30. This position passed quality control check.

BS2

High AC in GnomAd4 at 490 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TCOF1	NM_001371623.1 link	c.4332_4334delGAA	p.Lys1445del	disruptive_inframe_deletion	Exon 24 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.4332_4334delGAA	p.Lys1445del	disruptive_inframe_deletion	Exon 24 of 27		NM_001371623.1	ENSP00000493815.1		Q13428-3

Frequencies

GnomAD3 genomes

AF:

0.00322

AC:

490

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000652

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0114

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00440

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00313

AC:

720

AN:

229938

AF XY:

0.00298

show subpopulations

Gnomad AFR exome

AF:

0.000292

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00125

Gnomad EAS exome

AF:

0.0000577

Gnomad FIN exome

AF:

0.0109

Gnomad NFE exome

AF:

0.00378

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00346

AC:

5023

AN:

1453410

Hom.:

AF XY:

0.00336

AC XY:

2429

AN XY:

722212

show subpopulations

African (AFR)

AF:

0.000569

AC:

AN:

33414

American (AMR)

AF:

0.00182

AC:

AN:

43428

Ashkenazi Jewish (ASJ)

AF:

0.00135

AC:

AN:

25962

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39506

South Asian (SAS)

AF:

0.000235

AC:

AN:

85060

European-Finnish (FIN)

AF:

0.0112

AC:

579

AN:

51794

Middle Eastern (MID)

AF:

0.000703

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00372

AC:

4125

AN:

1108444

Other (OTH)

AF:

0.00268

AC:

161

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

304

609

913

1218

1522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

148

296

444

592

740

<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:

0.00322

AC:

490

AN:

152156

Hom.:

Cov.:

AF XY:

0.00363

AC XY:

270

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41514

American (AMR)

AF:

0.00203

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5148

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0114

AC:

121

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00440

AC:

299

AN:

68000

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

115

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00117

Hom.:

Bravo

AF:

0.00237

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:5

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Apr 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

TCOF1: PM4:Supporting, BS1 -

Feb 11, 2015

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 25, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 12444270) -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Treacher Collins syndrome 1

Benign:1

Jan 22, 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

PhyloP100

4.7

Mutation Taster

=53/47

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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