chr20-62006673-G-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_003185.4(TAF4):c.2060C>T(p.Ser687Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,596,170 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 Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
TAF4
NM_003185.4 missense
NM_003185.4 missense
Scores
1
4
14
Clinical Significance
Conservation
PhyloP100: 6.93
Genes affected
TAF4 (HGNC:11537): (TATA-box binding protein associated factor 4) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is transcription factor IID (TFIID), which binds to the core promoter to position the polymerase properly, serves as the scaffold for assembly of the remainder of the transcription complex, and acts as a channel for regulatory signals. TFIID is composed of the TATA-binding protein (TBP) and a group of evolutionarily conserved proteins known as TBP-associated factors or TAFs. TAFs may participate in basal transcription, serve as coactivators, function in promoter recognition or modify general transcription factors (GTFs) to facilitate complex assembly and transcription initiation. This gene encodes one of the larger subunits of TFIID that has been shown to potentiate transcriptional activation by retinoic acid, thyroid hormone and vitamin D3 receptors. In addition, this subunit interacts with the transcription factor CREB, which has a glutamine-rich activation domain, and binds to other proteins containing glutamine-rich regions. Aberrant binding to this subunit by proteins with expanded polyglutamine regions has been suggested as one of the pathogenetic mechanisms underlying a group of neurodegenerative disorders referred to as polyglutamine diseases. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.17664883).
BS2
High AC in GnomAdExome4 at 20 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TAF4 | NM_003185.4 | c.2060C>T | p.Ser687Leu | missense_variant | 7/15 | ENST00000252996.9 | |
TAF4 | XM_047440429.1 | c.944C>T | p.Ser315Leu | missense_variant | 8/16 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TAF4 | ENST00000252996.9 | c.2060C>T | p.Ser687Leu | missense_variant | 7/15 | 1 | NM_003185.4 | P1 | |
TAF4 | ENST00000488539.1 | c.101C>T | p.Ser34Leu | missense_variant | 2/5 | 5 | |||
TAF4 | ENST00000436129.2 | n.431C>T | non_coding_transcript_exon_variant | 3/11 | 2 | ||||
TAF4 | ENST00000609041.1 | n.323C>T | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000544 AC: 13AN: 238878Hom.: 0 AF XY: 0.0000691 AC XY: 9AN XY: 130318
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GnomAD4 exome AF: 0.0000139 AC: 20AN: 1443942Hom.: 0 Cov.: 30 AF XY: 0.0000126 AC XY: 9AN XY: 716518
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 07, 2023 | Variant summary: TAF4 c.2060C>T (p.Ser687Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.4e-05 in 238878 control chromosomes. To our knowledge, no occurrence of c.2060C>T in individuals affected with Intellectual Developmental Disorder, Autosomal Dominant 73 and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Uncertain
D;D
Polyphen
P;.
Vest4
MutPred
Loss of glycosylation at S687 (P = 0.0158);.;
MVP
MPC
ClinPred
T
GERP RS
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gMVP
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