chr2-9849441-T-TA
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1
The NM_005680.3(TAF1B):c.197dup(p.Asn66LysfsTer4) variant causes a frameshift change. The variant allele was found at a frequency of 0.0501 in 1,026,008 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)
Exomes 𝑓: 0.058 ( 0 hom. )
Consequence
TAF1B
NM_005680.3 frameshift
NM_005680.3 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.14
Genes affected
TAF1B (HGNC:11533): (TATA-box binding protein associated factor, RNA polymerase I subunit B) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes one of the SL1-specific TAFs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -8 ACMG points.
BA1
?
GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0788 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF1B | NM_005680.3 | c.197dup | p.Asn66LysfsTer4 | frameshift_variant | 3/15 | ENST00000263663.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF1B | ENST00000263663.10 | c.197dup | p.Asn66LysfsTer4 | frameshift_variant | 3/15 | 1 | NM_005680.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000227 AC: 33AN: 145660Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0583 AC: 51348AN: 880286Hom.: 0 Cov.: 28 AF XY: 0.0590 AC XY: 25576AN XY: 433588
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GnomAD4 genome ? AF: 0.000226 AC: 33AN: 145722Hom.: 0 Cov.: 32 AF XY: 0.000296 AC XY: 21AN XY: 70872
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Orofacial cleft 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Grupo de Genetica Humana, Facultad de Medicina - Universidad de La Sabana | Nov 22, 2022 | VUS producing a null variant (frameshift) in the TAF1B gene, which encodes one of the proteins in the assembly of the RNA polymerase I preinitiation complex. Although no association has been proposed for this variant with orofacial cleft, it is predicted to produce Loss of Function, which is a known mechanism of disease for this gene and is located in a functional domain (“B-reader”) of the encoded protein. Other variants in TAF1B have achieved genome-wide significance for nonsyndromic orofacial clefts in a GWAS study with more than 7,000 patients with non-syndromic orofacial cleft. - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at