Menu
GeneBe

rs1555971253

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_004606.5(TAF1):c.2773G>A(p.Asp925Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD Genomes project. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. D925D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 22)

Consequence

TAF1
NM_004606.5 missense

Scores

6
4
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 9.46
Variant links:
Genes affected
TAF1 (HGNC:11535): (TATA-box binding protein associated factor 1) Initiation of transcription by RNA polymerase II requires the activities of more than 70 polypeptides. The protein that coordinates these activities is the basal transcription factor 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 the largest subunit of TFIID. This subunit binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation. This subunit contains two independent protein kinase domains at the N- and C-terminals, but also possesses acetyltransferase activity and can act as a ubiquitin-activating/conjugating enzyme. Mutations in this gene result in Dystonia 3, torsion, X-linked, a dystonia-parkinsonism disorder. Alternative splicing of this gene results in multiple transcript variants. This gene is part of a complex transcription unit (TAF1/DYT3), wherein some transcript variants share exons with TAF1 as well as additional downstream DYT3 exons. [provided by RefSeq, Oct 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP2
Missense variant where missense usually causes diseases, TAF1

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
TAF1NM_004606.5 linkuse as main transcriptc.2773G>A p.Asp925Asn missense_variant 18/38 ENST00000423759.6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TAF1ENST00000423759.6 linkuse as main transcriptc.2773G>A p.Asp925Asn missense_variant 18/385 NM_004606.5 A2

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
Cov.:
28
GnomAD4 genome
Cov.:
22

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsFeb 24, 2016- -
Intellectual disability, X-linked, syndromic 33 Uncertain:1
Uncertain significance, no assertion criteria providedclinical testingGenome Medicine, Institute for Basic Research in Developmental DisabilitiesSep 23, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.98
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.74
Cadd
Pathogenic
28
Dann
Pathogenic
1.0
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.97
D;D;D
M_CAP
Uncertain
0.10
D
MetaRNN
Uncertain
0.67
D;D;D
MetaSVM
Benign
-1.0
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.91
D
PROVEAN
Pathogenic
-4.6
D;D;D
REVEL
Uncertain
0.29
Sift
Benign
0.072
T;T;T
Sift4G
Uncertain
0.0030
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.69
MutPred
0.30
.;Gain of MoRF binding (P = 0.0981);.;
MVP
0.80
MPC
2.5
ClinPred
1.0
D
GERP RS
5.0
Varity_R
0.76
gMVP
0.87

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1555971253; hg19: chrX-70609507; API