2-9868348-C-T

Variant names:

• chr2-9868348-C-T
• rs747452457
• NM_005680.3:c.472C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005680.3(TAF1B):​c.472C>T​(p.Pro158Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,868 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P158A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: TAF1B NM_005680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.88

Genes affected

TAF1B (HGNC:11533): (TATA-box binding protein associated factor, RNA polymerase I subunit B) Initiation of transcription by RNA polymerase I requires the formation of a complex composed of the TATA-binding protein (TBP) and three TBP-associated factors (TAFs) specific for RNA polymerase I. This complex, known as SL1, binds to the core promoter of ribosomal RNA genes to position the polymerase properly and acts as a channel for regulatory signals. This gene encodes one of the SL1-specific TAFs. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04407075).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TAF1B	NM_005680.3	c.472C>T	p.Pro158Ser	missense_variant	Exon 6 of 15	ENST00000263663.10	NP_005671.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TAF1B	ENST00000263663.10	c.472C>T	p.Pro158Ser	missense_variant	Exon 6 of 15	1	NM_005680.3	ENSP00000263663.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461868 Hom.: 0 Cov.: 31 AF XY: 0.00000963 AC XY: 7 AN XY: 727234

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000378

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	0.057
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.3
DANN	Benign	0.15
DEOGEN2	Benign	0.0076	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0019	N
LIST_S2	Benign	0.58	T
M_CAP	Benign	0.0019	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.38	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	1.6	N
REVEL	Benign	0.046
Sift	Benign	0.30	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.034
MutPred		0.13		Gain of phosphorylation at P158 (P = 0.0254);
MVP		0.15
MPC		0.11
ClinPred		0.17	T
GERP RS		-0.22
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.022
gMVP		0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs747452457; hg19: chr2-10008477;