Variant 10-103379720-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006951.5(TAF5):c.1226G>A(p.Ser409Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0073 in 1,606,738 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.0042 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 53 hom. )

Consequence

TAF5
NM_006951.5 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 4.79

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035065114).

BS2

High AC in GnomAd4 at 646 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF5	NM_006951.5 linkuse as main transcript	c.1226G>A	p.Ser409Asn	missense_variant	4/11	ENST00000369839.4	NP_008882.2
TAF5	NM_139052.3 linkuse as main transcript	c.1226G>A	p.Ser409Asn	missense_variant	4/10		NP_620640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF5	ENST00000369839.4 linkuse as main transcript	c.1226G>A	p.Ser409Asn	missense_variant	4/11	1	NM_006951.5	ENSP00000358854	P1	Q15542-1

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

646

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00133

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00210

Gnomad ASJ

AF:

0.0113

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0130

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00650

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.00544

AC:

1328

AN:

244248

Hom.:

AF XY:

0.00627

AC XY:

827

AN XY:

131958

show subpopulations

Gnomad AFR exome

AF:

0.000930

Gnomad AMR exome

AF:

0.00149

Gnomad ASJ exome

AF:

0.0100

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0134

Gnomad FIN exome

AF:

0.000278

Gnomad NFE exome

AF:

0.00661

Gnomad OTH exome

AF:

0.00656

GnomAD4 exome

AF:

0.00762

AC:

11078

AN:

1454470

Hom.:

Cov.:

AF XY:

0.00776

AC XY:

5609

AN XY:

723076

show subpopulations

Gnomad4 AFR exome

AF:

0.000943

Gnomad4 AMR exome

AF:

0.00175

Gnomad4 ASJ exome

AF:

0.00865

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0128

Gnomad4 FIN exome

AF:

0.000375

Gnomad4 NFE exome

AF:

0.00826

Gnomad4 OTH exome

AF:

0.00686

GnomAD4 genome

AF:

0.00424

AC:

646

AN:

152268

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

319

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00132

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.0113

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0131

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00650

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00666

Hom.:

Bravo

AF:

0.00416

TwinsUK

AF:

0.00593

AC:

ALSPAC

AF:

0.00960

AC:

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.00756

AC:

ExAC

AF:

0.00558

AC:

677

Asia WGS

AF:

0.00722

AC:

AN:

3478

EpiCase

AF:

0.00808

EpiControl

AF:

0.00754

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

LINK: link

Submissions by phenotype

not provided

Other:1

not provided, no classification provided

phenotyping only

GenomeConnect-Association for Creatine Deficiencies, Association for Creatine Deficiencies

Variant interpreted as Uncertain significance and reported on 06-08-2017 by GTR ID 1006. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect facilitates ClinVar submission from the Association for Creatine Deficiencies registry and does not attempt to reinterpret the variant. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.014

Eigen

Benign

-0.14

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.44

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.1

REVEL

Benign

0.048

Sift

Benign

0.42

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.18

MVP

0.53

MPC

0.71

ClinPred

0.012

GERP RS

5.6

Varity_R

0.13

gMVP

0.34

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.

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