chr18-26227063-G-A

Variant names:

• chr18-26227063-G-A
• rs78262333
• NM_005640.3:c.130G>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.130G>A​(p.Ala44Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TAF4B NM_005640.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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=0.12175104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF4B	NM_005640.3	c.130G>A	p.Ala44Thr	missense_variant	Exon 1 of 15	ENST00000269142.10	NP_005631.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF4B	ENST00000269142.10	c.130G>A	p.Ala44Thr	missense_variant	Exon 1 of 15	1	NM_005640.3	ENSP00000269142.6
TAF4B	ENST00000578121.5	c.130G>A	p.Ala44Thr	missense_variant	Exon 1 of 15	2		ENSP00000462980.1
TAF4B	ENST00000418698.3	n.130G>A		non_coding_transcript_exon_variant	Exon 1 of 16	5		ENSP00000389365.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443048 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 718124

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.46	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.0095	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	0.29	N;.
REVEL	Benign	0.021
Sift	Uncertain	0.013	D;.
Sift4G	Benign	0.25	T;T
Polyphen		0.80	P;.
Vest4		0.14
MutPred		0.33		Gain of phosphorylation at A44 (P = 0.0485);Gain of phosphorylation at A44 (P = 0.0485);
MVP		0.15
MPC		1.3
ClinPred		0.75	D
GERP RS		1.5
Varity_R		0.052
gMVP		0.32

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: rs78262333; hg19: chr18-23807027;