18-26227039-G-A

Position:

• chr18-26227039-G-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.106G>A​(p.Glu36Lys) 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. 12/21 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: 1.67

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=0.14422536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.106G>A	p.Glu36Lys	missense_variant	1/15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.106G>A	p.Glu36Lys	missense_variant	1/15	1	NM_005640.3	ENSP00000269142	P4
TAF4B	ENST00000578121.5	c.106G>A	p.Glu36Lys	missense_variant	1/15	2		ENSP00000462980	A2
TAF4B	ENST00000418698.3	c.106G>A	p.Glu36Lys	missense_variant, NMD_transcript_variant	1/16	5		ENSP00000389365

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

Aug 01, 2022

The c.106G>A (p.E36K) alteration is located in exon 1 (coding exon 1) of the TAF4B gene. This alteration results from a G to A substitution at nucleotide position 106, causing the glutamic acid (E) at amino acid position 36 to be replaced by a lysine (K). 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	0.14
BayesDel_addAF	Benign	-0.030	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.033
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.30	N
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.50	N;.
REVEL	Benign	0.038
Sift	Benign	0.070	T;.
Sift4G	Benign	0.74	T;T
Polyphen		0.44	B;.
Vest4		0.28
MutPred		0.36		Gain of sheet (P = 0.0011);Gain of sheet (P = 0.0011);
MVP		0.22
MPC		1.2
ClinPred		0.75	D
GERP RS		4.4
Varity_R		0.17
gMVP		0.47

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: chr18-23807003;