Variant X-78131686-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_015975.5(TAF9B):c.680C>T(p.Ser227Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,208,033 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 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 0.000027 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.000033 ( 0 hom. 10 hem. )

Consequence

TAF9B
NM_015975.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.74

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]

TAF9B links:

TAF9B (HGNC:):

TAF9B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30870733).

BS2

High Hemizygotes in GnomAdExome4 at 10 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF9B	NM_015975.5 linkuse as main transcript	c.680C>T	p.Ser227Leu	missense_variant	7/7	ENST00000341864.6	NP_057059.2	Q9HBM6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF9B	ENST00000341864.6 linkuse as main transcript	c.680C>T	p.Ser227Leu	missense_variant	7/7	1	NM_015975.5	ENSP00000339917.5		Q9HBM6
TAF9B	ENST00000480681.1 linkuse as main transcript	n.*35C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0000269

AC:

AN:

111511

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33711

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:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000164

AC:

AN:

183111

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

67569

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:

0.0000367

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000328

AC:

AN:

1096522

Hom.:

Cov.:

AF XY:

0.0000276

AC XY:

AN XY:

361942

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000284

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000994

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000381

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000269

AC:

AN:

111511

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33711

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:

0.0000565

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.0000165

AC:

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

Ambry Genetics

Apr 17, 2024

The c.680C>T (p.S227L) alteration is located in exon 7 (coding exon 7) of the TAF9B gene. This alteration results from a C to T substitution at nucleotide position 680, causing the serine (S) at amino acid position 227 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

0.13

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.51

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

M_CAP

Benign

0.0052

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-1.1

REVEL

Benign

0.21

Sift

Uncertain

0.022

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.27

MVP

0.62

MPC

0.18

ClinPred

0.40

GERP RS

3.3

Varity_R

0.22

gMVP

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over