Variant 8-119732010-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003184.4(TAF2):c.3514G>T(p.Asp1172Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TAF2
NM_003184.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.29

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23392987).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4 link	c.3514G>T	p.Asp1172Tyr	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.3514G>T	p.Asp1172Tyr	missense_variant	26/26	1	NM_003184.4	ENSP00000367406.2	Q6P1X5
TAF2	ENST00000686879.1 link	c.3670G>T	p.Asp1224Tyr	missense_variant	27/27			ENSP00000509206.1	A0A8I5KV60
TAF2	ENST00000685235.1 link	c.3559G>T	p.Asp1187Tyr	missense_variant	26/26			ENSP00000510174.1	A0A8I5QJR0
TAF2	ENST00000688645.1 link	c.3403G>T	p.Asp1135Tyr	missense_variant	25/25			ENSP00000509978.1	A0A8I5KSY6
TAF2	ENST00000523904.2 link	c.3400G>T	p.Asp1134Tyr	missense_variant	25/25	3		ENSP00000430832.2	H0YC37
TAF2	ENST00000690144 link	c.*645G>T		3_prime_UTR_variant	26/26			ENSP00000510548.1	A0A8I5KUQ2
TAF2	ENST00000685202.1 link	n.*1039G>T		non_coding_transcript_exon_variant	27/27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2906G>T		non_coding_transcript_exon_variant	26/26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3386G>T		non_coding_transcript_exon_variant	28/28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4981G>T		non_coding_transcript_exon_variant	25/25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3215G>T		non_coding_transcript_exon_variant	24/24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3232G>T		non_coding_transcript_exon_variant	27/27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3329G>T		non_coding_transcript_exon_variant	25/25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2159G>T		non_coding_transcript_exon_variant	25/25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2933G>T		non_coding_transcript_exon_variant	23/23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3121G>T		non_coding_transcript_exon_variant	26/26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2750G>T		non_coding_transcript_exon_variant	26/26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1926G>T		non_coding_transcript_exon_variant	26/26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3170G>T		non_coding_transcript_exon_variant	25/25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3380G>T		non_coding_transcript_exon_variant	25/25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3382G>T		non_coding_transcript_exon_variant	28/28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2901G>T		non_coding_transcript_exon_variant	25/25			ENSP00000509603.1	A0A8I5QJI9
TAF2	ENST00000685202.1 link	n.*1039G>T		3_prime_UTR_variant	27/27			ENSP00000509214.1	A0A8I5QJD7
TAF2	ENST00000685503.1 link	n.*2906G>T		3_prime_UTR_variant	26/26			ENSP00000509198.1	A0A8I5KXS3
TAF2	ENST00000685663.1 link	n.*3386G>T		3_prime_UTR_variant	28/28			ENSP00000508988.1	A0A8I5KUD2
TAF2	ENST00000685684.1 link	n.*4981G>T		3_prime_UTR_variant	25/25			ENSP00000509441.1	A0A8I5KY57
TAF2	ENST00000685824.1 link	n.*3215G>T		3_prime_UTR_variant	24/24			ENSP00000510262.1	A0A8I5KU60
TAF2	ENST00000685876.1 link	n.*3232G>T		3_prime_UTR_variant	27/27			ENSP00000510493.1	A0A8I5KUD2
TAF2	ENST00000685993.1 link	n.*3329G>T		3_prime_UTR_variant	25/25			ENSP00000510102.1	A0A8I5KU60
TAF2	ENST00000686098.1 link	n.*2159G>T		3_prime_UTR_variant	25/25			ENSP00000509102.1	A0A8I5KXP3
TAF2	ENST00000688037.1 link	n.*2933G>T		3_prime_UTR_variant	23/23			ENSP00000510169.1	A0A8I5KRI4
TAF2	ENST00000689919.1 link	n.*3121G>T		3_prime_UTR_variant	26/26			ENSP00000510768.1	A0A8I5KUD2
TAF2	ENST00000690808.1 link	n.*2750G>T		3_prime_UTR_variant	26/26			ENSP00000509791.1	A0A8I5KVC1
TAF2	ENST00000690922.1 link	n.*1926G>T		3_prime_UTR_variant	26/26			ENSP00000509498.1	A0A8I5KPW0
TAF2	ENST00000691880.1 link	n.*3170G>T		3_prime_UTR_variant	25/25			ENSP00000508515.1	A0A8I5KNG3
TAF2	ENST00000692518.1 link	n.*3380G>T		3_prime_UTR_variant	25/25			ENSP00000508959.1	A0A8I5KU60
TAF2	ENST00000692707.1 link	n.*3382G>T		3_prime_UTR_variant	28/28			ENSP00000509024.1	A0A8I5KUD2
TAF2	ENST00000692916.1 link	n.*2901G>T		3_prime_UTR_variant	25/25			ENSP00000509603.1	A0A8I5QJI9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 06, 2023

The c.3514G>T (p.D1172Y) alteration is located in exon 26 (coding exon 26) of the TAF2 gene. This alteration results from a G to T substitution at nucleotide position 3514, causing the aspartic acid (D) at amino acid position 1172 to be replaced by a tyrosine (Y). 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

Pathogenic

0.60

BayesDel_addAF

Benign

-0.040

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.023

T;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

D;D

M_CAP

Benign

0.027

MetaRNN

Benign

0.23

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;.

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-2.4

N;D

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0070

D;T

Polyphen

0.89

P;.

Vest4

0.40

MutPred

0.24

Gain of phosphorylation at D1172 (P = 0.0152);.;

MVP

0.093

MPC

0.95

ClinPred

0.77

GERP RS

6.0

Varity_R

0.23

gMVP

0.25

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

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