X-78139604-G-A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_015975.5(TAF9B):​c.8C>T​(p.Ser3Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000306 in 1,210,351 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 12 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)
Exomes 𝑓: 0.000033 ( 0 hom. 12 hem. )

Consequence

TAF9B
NM_015975.5 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48
Variant links:
Genes affected
TAF9B (HGNC:17306): (TATA-box binding protein associated factor 9b) 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 a protein that is similar to one of the small subunits of TFIID, TBP-associated factor 9, and is also a subunit of TFIID. TAF9 and TAF9b share some functions but also have distinct roles in the transcriptional regulatory process. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2097038).
BS2
High Hemizygotes in GnomAdExome4 at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAF9BNM_015975.5 linkc.8C>T p.Ser3Leu missense_variant 1/7 ENST00000341864.6 NP_057059.2 Q9HBM6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAF9BENST00000341864.6 linkc.8C>T p.Ser3Leu missense_variant 1/71 NM_015975.5 ENSP00000339917.5 Q9HBM6
TAF9BENST00000480681.1 linkn.19C>T non_coding_transcript_exon_variant 1/63

Frequencies

GnomAD3 genomes
AF:
0.00000887
AC:
1
AN:
112728
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34880
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000188
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000110
AC:
2
AN:
182281
Hom.:
0
AF XY:
0.0000150
AC XY:
1
AN XY:
66785
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000246
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000328
AC:
36
AN:
1097623
Hom.:
0
Cov.:
30
AF XY:
0.0000331
AC XY:
12
AN XY:
363053
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000392
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
AF:
0.00000887
AC:
1
AN:
112728
Hom.:
0
Cov.:
23
AF XY:
0.00
AC XY:
0
AN XY:
34880
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000188
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000119

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 submitterclinical testingAmbry GeneticsApr 01, 2024The c.8C>T (p.S3L) alteration is located in exon 1 (coding exon 1) of the TAF9B gene. This alteration results from a C to T substitution at nucleotide position 8, causing the serine (S) at amino acid position 3 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.60
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.17
T
FATHMM_MKL
Benign
0.75
D
LIST_S2
Benign
0.77
T
M_CAP
Pathogenic
0.35
D
MetaRNN
Benign
0.21
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-2.0
N
REVEL
Benign
0.079
Sift
Benign
0.051
T
Sift4G
Benign
0.10
T
Polyphen
0.061
B
Vest4
0.32
MutPred
0.34
Loss of phosphorylation at S3 (P = 0.0168);
MVP
0.64
MPC
0.18
ClinPred
0.33
T
GERP RS
3.7
Varity_R
0.088
gMVP
0.60

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: rs782131212; hg19: chrX-77395101; API