18-26227124-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005640.3(TAF4B):c.191C>A(p.Ser64Tyr) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.06

Genes affected

TAF4B (HGNC:11538): (TATA-box binding protein associated factor 4b) TATA binding protein (TBP) and TBP-associated factors (TAFs) participate in the formation of the TFIID protein complex, which is involved in initiation of transcription of genes by RNA polymerase II. This gene encodes a cell type-specific TAF that may be responsible for mediating transcription by a subset of activators in B cells. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jun 2014]

ACMG classification

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=0.14655432).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF4B	NM_005640.3	c.191C>A	p.Ser64Tyr	missense_variant	1/15	ENST00000269142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4B	ENST00000269142.10	c.191C>A	p.Ser64Tyr	missense_variant	1/15	1	NM_005640.3	P4
TAF4B	ENST00000578121.5	c.191C>A	p.Ser64Tyr	missense_variant	1/15	2		A2
TAF4B	ENST00000418698.3	c.191C>A	p.Ser64Tyr	missense_variant, NMD_transcript_variant	1/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 13, 2024

The c.191C>A (p.S64Y) alteration is located in exon 1 (coding exon 1) of the TAF4B gene. This alteration results from a C to A substitution at nucleotide position 191, causing the serine (S) at amino acid position 64 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	Benign	0.13
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
Cadd	Benign	21
Dann	Benign	0.90
DEOGEN2	Benign	0.063	T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.74	T;T
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.3	N;.
REVEL	Benign	0.027
Sift	Uncertain	0.012	D;.
Sift4G	Uncertain	0.027	D;D
Polyphen		0.68	P;.
Vest4		0.26
MutPred		0.27		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);
MVP		0.15
MPC		1.7
ClinPred		0.90	D
GERP RS		3.4
Varity_R		0.12
gMVP		0.27

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: chr18-23807088;