8-119732035-A-C

Position:

• chr8-119732035-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000378164.7(TAF2):​c.3489T>G​(p.His1163Gln) variant causes a missense change involving the alteration of a non-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 ENST00000378164.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0420

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
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), TAF2. . Gene score misZ 2.7836 (greater than the threshold 3.09). Trascript score misZ 3.5113 (greater than threshold 3.09). GenCC has associacion of gene with microcephaly-thin corpus callosum-intellectual disability syndrome.
• BP4: Computational evidence support a benign effect (MetaRNN=0.21725363).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF2	NM_003184.4	c.3489T>G	p.His1163Gln	missense_variant	26/26	ENST00000378164.7	NP_003175.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF2	ENST00000378164.7	c.3489T>G	p.His1163Gln	missense_variant	26/26	1	NM_003184.4	ENSP00000367406	P1

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 22, 2021

The c.3489T>G (p.H1163Q) alteration is located in exon 26 (coding exon 26) of the TAF2 gene. This alteration results from a T to G substitution at nucleotide position 3489, causing the histidine (H) at amino acid position 1163 to be replaced by a glutamine (Q). The p.H1163Q alteration is predicted to be tolerated by in silico analysis. 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	0.98
BayesDel_addAF	Benign	-0.073	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.15	T;.
Eigen	Benign	-0.86
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.90	L;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.7	D;D
REVEL	Uncertain	0.32
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0030	D;D
Polyphen		0.93	P;.
Vest4		0.50
MutPred		0.16		Gain of solvent accessibility (P = 0.0155);.;
MVP		0.52
MPC		1.2
ClinPred		0.89	D
GERP RS		-9.7
Varity_R		0.76
gMVP		0.17

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.

Other links and lift over

hg19: chr8-120744275;