chr10-103368414-A-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006951.5(TAF5):c.425A>T(p.Glu142Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000464 in 1,508,678 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TAF5
NM_006951.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.97

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12503958).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5 link	c.425A>T	p.Glu142Val	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2	Q15542-1
TAF5	NM_139052.3 link	c.425A>T	p.Glu142Val	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.425A>T	p.Glu142Val	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3		Q15542-1

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148822

Hom.:

Cov.:

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:

0.0000446

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000554

AC:

AN:

180630

AF XY:

0.00

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:

0.0000127

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1359856

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

675462

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29784

American (AMR)

AF:

0.00

AC:

AN:

38694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22760

East Asian (EAS)

AF:

0.00

AC:

AN:

35338

South Asian (SAS)

AF:

0.00

AC:

AN:

82480

European-Finnish (FIN)

AF:

0.00

AC:

AN:

29996

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4166

European-Non Finnish (NFE)

AF:

0.00000377

AC:

AN:

1062160

Other (OTH)

AF:

0.00

AC:

AN:

54478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148822

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72660

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40664

American (AMR)

AF:

0.00

AC:

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3436

East Asian (EAS)

AF:

0.00

AC:

AN:

4832

South Asian (SAS)

AF:

0.00

AC:

AN:

4282

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10104

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000446

AC:

AN:

67212

Other (OTH)

AF:

0.00

AC:

AN:

2074

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.425A>T (p.E142V) alteration is located in exon 1 (coding exon 1) of the TAF5 gene. This alteration results from a A to T substitution at nucleotide position 425, causing the glutamic acid (E) at amino acid position 142 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

0.19

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.012

Eigen

Benign

-0.53

Eigen_PC

Benign

-0.41

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.56

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

6.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.82

REVEL

Benign

0.12

Sift

Uncertain

0.013

Sift4G

Benign

0.25

Polyphen

0.0

Vest4

0.25

MutPred

0.15

Gain of MoRF binding (P = 0.0759);

MVP

0.47

MPC

0.91

ClinPred

0.27

GERP RS

3.0

PromoterAI

0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.21

gMVP

0.33

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

chr10-103368414-A-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over