X-78138870-T-C

Variant summary

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

The NM_015975.5(TAF9B):ā€‹c.106A>Gā€‹(p.Ile36Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000273 in 1,208,531 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 11 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00017 ( 0 hom., 7 hem., cov: 24)
Exomes š‘“: 0.000013 ( 0 hom. 4 hem. )

Consequence

TAF9B
NM_015975.5 missense

Scores

1
3
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.71
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=0.11735761).
BS2
High Hemizygotes in GnomAd4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TAF9BNM_015975.5 linkc.106A>G p.Ile36Val missense_variant 2/7 ENST00000341864.6 NP_057059.2 Q9HBM6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TAF9BENST00000341864.6 linkc.106A>G p.Ile36Val missense_variant 2/71 NM_015975.5 ENSP00000339917.5 Q9HBM6
TAF9BENST00000480681.1 linkn.117A>G non_coding_transcript_exon_variant 2/63

Frequencies

GnomAD3 genomes
AF:
0.000168
AC:
19
AN:
113133
Hom.:
0
Cov.:
24
AF XY:
0.000198
AC XY:
7
AN XY:
35271
show subpopulations
Gnomad AFR
AF:
0.000610
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000495
AC:
9
AN:
181894
Hom.:
0
AF XY:
0.0000452
AC XY:
3
AN XY:
66358
show subpopulations
Gnomad AFR exome
AF:
0.000534
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000146
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000128
AC:
14
AN:
1095398
Hom.:
0
Cov.:
28
AF XY:
0.0000111
AC XY:
4
AN XY:
360828
show subpopulations
Gnomad4 AFR exome
AF:
0.000228
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000152
GnomAD4 genome
AF:
0.000168
AC:
19
AN:
113133
Hom.:
0
Cov.:
24
AF XY:
0.000198
AC XY:
7
AN XY:
35271
show subpopulations
Gnomad4 AFR
AF:
0.000610
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:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000185
Hom.:
1
Bravo
AF:
0.000162
ESP6500AA
AF:
0.000782
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000107
AC:
13

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 GeneticsJan 22, 2024The c.106A>G (p.I36V) alteration is located in exon 2 (coding exon 2) of the TAF9B gene. This alteration results from a A to G substitution at nucleotide position 106, causing the isoleucine (I) at amino acid position 36 to be replaced by a valine (V). 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
0.14
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.64
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.11
T
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.010
T
MetaRNN
Benign
0.12
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.86
L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.59
N
REVEL
Benign
0.041
Sift
Benign
0.15
T
Sift4G
Benign
0.31
T
Polyphen
0.0090
B
Vest4
0.31
MVP
0.61
MPC
0.091
ClinPred
0.055
T
GERP RS
5.0
Varity_R
0.26
gMVP
0.37

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: rs143257195; hg19: chrX-77394367; API