Genetic Variant NM_006951.5:c.425A>C (chr10-103368414-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006951.5(TAF5):c.425A>C(p.Glu142Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000294 in 1,359,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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. E142V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

TAF5
NM_006951.5 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10310593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF5	NM_006951.5 link	c.425A>C	p.Glu142Ala	missense_variant	Exon 1 of 11	ENST00000369839.4	NP_008882.2	Q15542-1
TAF5	NM_139052.3 link	c.425A>C	p.Glu142Ala	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>C	p.Glu142Ala	missense_variant	Exon 1 of 11	1	NM_006951.5	ENSP00000358854.3		Q15542-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000111

AC:

AN:

180630

AF XY:

0.0000198

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:

0.0000253

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000294

AC:

AN:

1359856

Hom.:

Cov.:

AF XY:

0.00000592

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:

0.000240

AC:

AN:

4166

European-Non Finnish (NFE)

AF:

0.00000282

AC:

AN:

1062160

Other (OTH)

AF:

0.00

AC:

AN:

54478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000886

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0083

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.47

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.59

M_CAP

Benign

0.054

MetaRNN

Benign

0.10

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

6.0

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.66

REVEL

Benign

0.13

Sift

Benign

0.053

Sift4G

Benign

0.67

Polyphen

0.0

Vest4

0.15

MutPred

0.10

Gain of MoRF binding (P = 0.0794);

MVP

0.42

MPC

0.81

ClinPred

0.16

GERP RS

3.0

PromoterAI

-0.020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.11

gMVP

0.23

Mutation Taster

=91/9

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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NM_006951.5:c.425A>C

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