rs199890846
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001371623.1(TCOF1):c.4023G>A(p.Lys1341=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000023 in 1,610,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
TCOF1
NM_001371623.1 synonymous
NM_001371623.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 2.29
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.75).
BP6
?
Variant 5-150396520-G-A is Benign according to our data. Variant chr5-150396520-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 543945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=2.29 with no splicing effect.
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TCOF1 | NM_001371623.1 | c.4023G>A | p.Lys1341= | synonymous_variant | 24/27 | ENST00000643257.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TCOF1 | ENST00000643257.2 | c.4023G>A | p.Lys1341= | synonymous_variant | 24/27 | NM_001371623.1 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152178Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000138 AC: 33AN: 238820Hom.: 0 AF XY: 0.000116 AC XY: 15AN XY: 129810
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GnomAD4 exome AF: 0.0000213 AC: 31AN: 1457798Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 724912
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152296Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74462
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 01, 2020 | - - |
Treacher Collins syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2017 | - - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at