chr8-119732159-C-T

Position:

chr8-119732159-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003184.4(TAF2):c.3365G>A(p.Ser1122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0691 in 1,613,680 control chromosomes in the GnomAD database, including 5,010 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.098 ( 1089 hom., cov: 33)

Exomes 𝑓: 0.066 ( 3921 hom. )

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.19

Variant links:

Genes affected

TAF2 (HGNC:11536): (TATA-box binding protein associated factor 2) 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 one of the larger subunits of TFIID that is stably associated with the TFIID complex. It contributes to interactions at and downstream of the transcription initiation site, interactions that help determine transcription complex response to activators. [provided by RefSeq, Jul 2008]

TAF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.4427E-4).

BP6

Variant 8-119732159-C-T is Benign according to our data. Variant chr8-119732159-C-T is described in ClinVar as [Benign]. Clinvar id is 1170266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.3365G>A	p.Ser1122Asn	missense_variant	26/26	ENST00000378164.7	NP_003175.2	Q6P1X5B3KMD8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TAF2	ENST00000378164.7 link	c.3365G>A	p.Ser1122Asn	missense_variant	26/26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.3521G>A	p.Ser1174Asn	missense_variant	27/27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.3410G>A	p.Ser1137Asn	missense_variant	26/26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.3254G>A	p.Ser1085Asn	missense_variant	25/25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.3251G>A	p.Ser1084Asn	missense_variant	25/25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144 link	c.*496G>A		3_prime_UTR_variant	26/26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.*890G>A		non_coding_transcript_exon_variant	27/27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2757G>A		non_coding_transcript_exon_variant	26/26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3237G>A		non_coding_transcript_exon_variant	28/28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4832G>A		non_coding_transcript_exon_variant	25/25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3066G>A		non_coding_transcript_exon_variant	24/24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3083G>A		non_coding_transcript_exon_variant	27/27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3180G>A		non_coding_transcript_exon_variant	25/25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2010G>A		non_coding_transcript_exon_variant	25/25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2784G>A		non_coding_transcript_exon_variant	23/23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689164.1 link	n.*3983G>A		non_coding_transcript_exon_variant	24/24			ENSP00000508729.1	A0A8I5KR26
TAF2	ENST00000689919.1 link	n.*2972G>A		non_coding_transcript_exon_variant	26/26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2601G>A		non_coding_transcript_exon_variant	26/26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1777G>A		non_coding_transcript_exon_variant	26/26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3021G>A		non_coding_transcript_exon_variant	25/25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3231G>A		non_coding_transcript_exon_variant	25/25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3233G>A		non_coding_transcript_exon_variant	28/28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2752G>A		non_coding_transcript_exon_variant	25/25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685202.1 link	n.*890G>A		3_prime_UTR_variant	27/27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2757G>A		3_prime_UTR_variant	26/26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3237G>A		3_prime_UTR_variant	28/28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4832G>A		3_prime_UTR_variant	25/25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3066G>A		3_prime_UTR_variant	24/24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3083G>A		3_prime_UTR_variant	27/27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3180G>A		3_prime_UTR_variant	25/25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2010G>A		3_prime_UTR_variant	25/25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2784G>A		3_prime_UTR_variant	23/23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689164.1 link	n.*3983G>A		3_prime_UTR_variant	24/24			ENSP00000508729.1	A0A8I5KR26
TAF2	ENST00000689919.1 link	n.*2972G>A		3_prime_UTR_variant	26/26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2601G>A		3_prime_UTR_variant	26/26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1777G>A		3_prime_UTR_variant	26/26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3021G>A		3_prime_UTR_variant	25/25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3231G>A		3_prime_UTR_variant	25/25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3233G>A		3_prime_UTR_variant	28/28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2752G>A		3_prime_UTR_variant	25/25			ENSP00000509603.1	A0A8I5QJI9

Frequencies

GnomAD3 genomes

AF:

0.0976

AC:

14838

AN:

152078

Hom.:

1089

Cov.:

show subpopulations

Gnomad AFR

AF:

0.202

Gnomad AMI

AF:

0.0866

Gnomad AMR

AF:

0.0404

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0371

Gnomad FIN

AF:

0.0758

Gnomad MID

AF:

0.0446

Gnomad NFE

AF:

0.0664

Gnomad OTH

AF:

0.0803

GnomAD3 exomes

AF:

0.0619

AC:

15569

AN:

251316

Hom.:

797

AF XY:

0.0590

AC XY:

8007

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0409

Gnomad ASJ exome

AF:

0.0265

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.0751

Gnomad NFE exome

AF:

0.0639

Gnomad OTH exome

AF:

0.0498

GnomAD4 exome

AF:

0.0661

AC:

96625

AN:

1461484

Hom.:

3921

Cov.:

AF XY:

0.0650

AC XY:

47251

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.210

Gnomad4 AMR exome

AF:

0.0412

Gnomad4 ASJ exome

AF:

0.0256

Gnomad4 EAS exome

AF:

0.000176

Gnomad4 SAS exome

AF:

0.0414

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.0677

Gnomad4 OTH exome

AF:

0.0664

GnomAD4 genome

AF:

0.0976

AC:

14850

AN:

152196

Hom.:

1089

Cov.:

AF XY:

0.0943

AC XY:

7021

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.202

Gnomad4 AMR

AF:

0.0404

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0363

Gnomad4 FIN

AF:

0.0758

Gnomad4 NFE

AF:

0.0664

Gnomad4 OTH

AF:

0.0795

Alfa

AF:

0.0623

Hom.:

983

Bravo

AF:

0.0989

TwinsUK

AF:

0.0701

AC:

260

ALSPAC

AF:

0.0664

AC:

256

ESP6500AA

AF:

0.208

AC:

918

ESP6500EA

AF:

0.0629

AC:

541

ExAC

AF:

0.0659

AC:

7996

Asia WGS

AF:

0.0250

AC:

AN:

3478

EpiCase

AF:

0.0564

EpiControl

AF:

0.0560

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 25, 2024	- -

TAF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.0093

T;.

Eigen

Benign

-0.78

Eigen_PC

Benign

-0.67

FATHMM_MKL

Benign

0.093

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.00084

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.46

N;.

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.63

N;N

REVEL

Benign

0.057

Sift

Benign

0.51

T;T

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.0050

MPC

0.38

ClinPred

0.00053

GERP RS

3.2

Varity_R

0.034

gMVP

0.066

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