NM_001371623.1:c.108G>A
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3
The NM_001371623.1(TCOF1):c.108G>A(p.Gln36Gln) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.00000657 in 152,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Consequence
TCOF1
NM_001371623.1 splice_region, synonymous
NM_001371623.1 splice_region, synonymous
Scores
2
Splicing: ADA: 0.9974
2
Clinical Significance
Conservation
PhyloP100: 4.74
Publications
0 publications found
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 1Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P
- Treacher-Collins syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF. No scorers claiming Uncertain. Scorers claiming Benign: max_spliceai.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001371623.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TCOF1 | MANE Select | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 27 | NP_001358552.1 | Q13428-3 | ||
| TCOF1 | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 27 | NP_001128715.1 | Q13428-1 | |||
| TCOF1 | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 26 | NP_001128716.1 | Q13428-7 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| TCOF1 | MANE Select | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 27 | ENSP00000493815.1 | Q13428-3 | ||
| TCOF1 | TSL:1 | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 26 | ENSP00000421655.2 | Q13428-1 | ||
| TCOF1 | TSL:1 | c.108G>A | p.Gln36Gln | splice_region synonymous | Exon 1 of 26 | ENSP00000325223.6 | Q13428-2 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152180Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152180
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome 0.00000657 AC: 1AN: 152294Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74464 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
152294
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74464
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
1
AN:
41570
American (AMR)
AF:
AC:
0
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
0
AN:
5162
South Asian (SAS)
AF:
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
AC:
0
AN:
10622
Middle Eastern (MID)
AF:
AC:
0
AN:
290
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68020
Other (OTH)
AF:
AC:
0
AN:
2114
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.325
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
1
-
Treacher Collins syndrome 1 (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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