18-26227271-C-T

Variant summary

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

The NM_005640.3(TAF4B):c.338C>T(p.Pro113Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,234 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.72

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3224349).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TAF4B	NM_005640.3	c.338C>T	p.Pro113Leu	missense_variant	1/15	ENST00000269142.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TAF4B	ENST00000269142.10	c.338C>T	p.Pro113Leu	missense_variant	1/15	1	NM_005640.3	P4
TAF4B	ENST00000578121.5	c.338C>T	p.Pro113Leu	missense_variant	1/15	2		A2
TAF4B	ENST00000418698.3	c.338C>T	p.Pro113Leu	missense_variant, NMD_transcript_variant	1/16	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460234 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726454

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jan 27, 2022

The c.338C>T (p.P113L) alteration is located in exon 1 (coding exon 1) of the TAF4B gene. This alteration results from a C to T substitution at nucleotide position 338, causing the proline (P) at amino acid position 113 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	Benign	0.12
BayesDel_addAF	Benign	-0.012	T
BayesDel_noAF	Benign	-0.26
Cadd	Uncertain	25
Dann	Uncertain	0.98
DEOGEN2	Uncertain	0.56	D;T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.89	D;D
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.32	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Pathogenic	-5.5	D;.
REVEL	Benign	0.18
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		0.0050	B;.
Vest4		0.43
MutPred		0.52		Loss of disorder (P = 0.0222);Loss of disorder (P = 0.0222);
MVP		0.32
MPC		1.5
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.52
gMVP		0.54

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

Other links and lift over

dbSNP: rs2055592386; hg19: chr18-23807235;