Genetic Variant TAF5:p.Thr9Lys (chr10-103368015-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_006951.5(TAF5):c.26C>A(p.Thr9Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000107 in 1,312,862 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T9M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TAF5
NM_006951.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.50

Publications

0 publications found

Variant links:

Genes affected

TAF5 (HGNC:11539): (TATA-box binding protein associated factor 5) 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 an integral subunit of TFIID associated with all transcriptionally competent forms of that complex. This subunit interacts strongly with two TFIID subunits that show similarity to histones H3 and H4, and it may participate in forming a nucleosome-like core in the TFIID complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

TAF5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11423269).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2	Q15542-1
TAF5	NM_139052.3 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 1 of 10		NP_620640.1	Q15542-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF5	ENST00000369839.4 link	c.26C>A	p.Thr9Lys	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3		Q15542-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000141

AC:

AN:

70796

AF XY:

0.0000246

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000359

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1312862

Hom.:

Cov.:

AF XY:

0.00000929

AC XY:

AN XY:

645908

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26258

American (AMR)

AF:

0.00

AC:

AN:

22708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22348

East Asian (EAS)

AF:

0.00

AC:

AN:

28602

South Asian (SAS)

AF:

0.00

AC:

AN:

70988

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36442

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4640

European-Non Finnish (NFE)

AF:

0.0000134

AC:

AN:

1046642

Other (OTH)

AF:

0.00

AC:

AN:

54234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.043

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.013

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.63

M_CAP

Benign

0.026

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.84

MutationAssessor

Benign

0.0

PhyloP100

4.5

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.30

REVEL

Benign

0.077

Sift

Pathogenic

0.0

Sift4G

Benign

0.25

Polyphen

0.15

Vest4

0.34

MutPred

0.13

Gain of ubiquitination at T9 (P = 0.0025);

MVP

0.20

MPC

1.9

ClinPred

0.52

GERP RS

3.4

PromoterAI

0.041

Neutral

(source)

Varity_R

0.42

gMVP

0.22

Mutation Taster

=86/14

polymorphism

(source)

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

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10-103368015-C-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over