8-119731940-G-A

Variant names:

• chr8-119731940-G-A
• NM_003184.4:c.3584C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003184.4(TAF2):​c.3584C>T​(p.Pro1195Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 33)
• Consequence: TAF2 NM_003184.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.92

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37158096).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF2	NM_003184.4	c.3584C>T	p.Pro1195Leu	missense_variant	Exon 26 of 26	ENST00000378164.7	NP_003175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF2	ENST00000378164.7	c.3584C>T	p.Pro1195Leu	missense_variant	Exon 26 of 26	1	NM_003184.4	ENSP00000367406.2
TAF2	ENST00000686879.1	c.3740C>T	p.Pro1247Leu	missense_variant	Exon 27 of 27			ENSP00000509206.1
TAF2	ENST00000685235.1	c.3629C>T	p.Pro1210Leu	missense_variant	Exon 26 of 26			ENSP00000510174.1
TAF2	ENST00000688645.1	c.3473C>T	p.Pro1158Leu	missense_variant	Exon 25 of 25			ENSP00000509978.1
TAF2	ENST00000523904.2	c.3470C>T	p.Pro1157Leu	missense_variant	Exon 25 of 25	3		ENSP00000430832.2
TAF2	ENST00000690144	c.*715C>T		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510548.1
TAF2	ENST00000685202.1	n.*1109C>T		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000509214.1
TAF2	ENST00000685503.1	n.*2976C>T		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*3456C>T		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*5051C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*3285C>T		non_coding_transcript_exon_variant	Exon 24 of 24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*3302C>T		non_coding_transcript_exon_variant	Exon 27 of 27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*3399C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000510102.1
TAF2	ENST00000686098.1	n.*2229C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509102.1
TAF2	ENST00000688037.1	n.*3003C>T		non_coding_transcript_exon_variant	Exon 23 of 23			ENSP00000510169.1
TAF2	ENST00000689919.1	n.*3191C>T		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*2820C>T		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509791.1
TAF2	ENST00000690922.1	n.*1996C>T		non_coding_transcript_exon_variant	Exon 26 of 26			ENSP00000509498.1
TAF2	ENST00000691880.1	n.*3240C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*3450C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*3452C>T		non_coding_transcript_exon_variant	Exon 28 of 28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*2971C>T		non_coding_transcript_exon_variant	Exon 25 of 25			ENSP00000509603.1
TAF2	ENST00000685202.1	n.*1109C>T		3_prime_UTR_variant	Exon 27 of 27			ENSP00000509214.1
TAF2	ENST00000685503.1	n.*2976C>T		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509198.1
TAF2	ENST00000685663.1	n.*3456C>T		3_prime_UTR_variant	Exon 28 of 28			ENSP00000508988.1
TAF2	ENST00000685684.1	n.*5051C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509441.1
TAF2	ENST00000685824.1	n.*3285C>T		3_prime_UTR_variant	Exon 24 of 24			ENSP00000510262.1
TAF2	ENST00000685876.1	n.*3302C>T		3_prime_UTR_variant	Exon 27 of 27			ENSP00000510493.1
TAF2	ENST00000685993.1	n.*3399C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000510102.1
TAF2	ENST00000686098.1	n.*2229C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509102.1
TAF2	ENST00000688037.1	n.*3003C>T		3_prime_UTR_variant	Exon 23 of 23			ENSP00000510169.1
TAF2	ENST00000689919.1	n.*3191C>T		3_prime_UTR_variant	Exon 26 of 26			ENSP00000510768.1
TAF2	ENST00000690808.1	n.*2820C>T		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509791.1
TAF2	ENST00000690922.1	n.*1996C>T		3_prime_UTR_variant	Exon 26 of 26			ENSP00000509498.1
TAF2	ENST00000691880.1	n.*3240C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508515.1
TAF2	ENST00000692518.1	n.*3450C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000508959.1
TAF2	ENST00000692707.1	n.*3452C>T		3_prime_UTR_variant	Exon 28 of 28			ENSP00000509024.1
TAF2	ENST00000692916.1	n.*2971C>T		3_prime_UTR_variant	Exon 25 of 25			ENSP00000509603.1
TAF2	ENST00000689164.1	n.*4202C>T		downstream_gene_variant				ENSP00000508729.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Nov 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3584C>T (p.P1195L) alteration is located in exon 26 (coding exon 26) of the TAF2 gene. This alteration results from a C to T substitution at nucleotide position 3584, causing the proline (P) at amino acid position 1195 to be replaced by a leucine (L). 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	0.64
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.022	T;.
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Uncertain	0.090	D
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	N;D
REVEL	Benign	0.26
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.64
MutPred		0.17		Loss of relative solvent accessibility (P = 0.0071);.;
MVP		0.44
MPC		0.83
ClinPred		0.86	D
GERP RS		5.9
Varity_R		0.29
gMVP		0.30

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-120744180;