rs2056257982

Variant names:

• chr18-26267585-A-G
• rs2056257982
• NM_005640.3:c.559A>G

Variant summary

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

The NM_005640.3(TAF4B):​c.559A>G​(p.Thr187Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,796 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.784

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=0.09766859).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.559A>G	p.Thr187Ala	missense_variant	Exon 3 of 15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.559A>G	p.Thr187Ala	missense_variant	Exon 3 of 15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.559A>G	p.Thr187Ala	missense_variant	Exon 3 of 15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.559A>G		non_coding_transcript_exon_variant	Exon 3 of 16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461796 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727196

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: 0.00000360

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

Aug 20, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.559A>G (p.T187A) alteration is located in exon 3 (coding exon 3) of the TAF4B gene. This alteration results from a A to G substitution at nucleotide position 559, causing the threonine (T) at amino acid position 187 to be replaced by an alanine (A). 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	0.076
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	16
DANN	Benign	0.94
DEOGEN2	Benign	0.086	T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.076
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.56	T;T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-1.1	N;.
REVEL	Benign	0.062
Sift	Benign	0.35	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.0010	B;.
Vest4		0.18
MutPred		0.21		Loss of glycosylation at T187 (P = 0.0191);Loss of glycosylation at T187 (P = 0.0191);
MVP		0.17
MPC		0.038
ClinPred		0.29	T
GERP RS		4.5
Varity_R		0.055
gMVP		0.34

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: rs2056257982; hg19: chr18-23847549; COSMIC: COSV99300242; COSMIC: COSV99300242;