rs776045935

Variant names:

• chr2-9868346-C-A
• rs776045935
• NM_005680.3:c.470C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-9868346-C-A
• chr2-9868346-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005680.3(TAF1B):​c.470C>A​(p.Pro157His) 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. 16/22 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. P157L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1B NM_005680.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0410
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04164642).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005680.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1B	NM_005680.3	MANE Select	c.470C>A	p.Pro157His	missense	Exon 6 of 15	NP_005671.3	Q53T94-1
	TAF1B	NM_001318976.1		c.-142C>A		5_prime_UTR	Exon 7 of 15	NP_001305905.1	Q53T94
	TAF1B	NM_001318977.1		c.-142C>A		5_prime_UTR	Exon 6 of 14	NP_001305906.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1B	ENST00000263663.10	TSL:1 MANE Select	c.470C>A	p.Pro157His	missense	Exon 6 of 15	ENSP00000263663.4	Q53T94-1
	TAF1B	ENST00000944452.1		c.470C>A	p.Pro157His	missense	Exon 6 of 16	ENSP00000614511.1
	TAF1B	ENST00000402170.5	TSL:5	n.530C>A		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	8.6
DANN	Benign	0.95
DEOGEN2	Benign	0.013	T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.044	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.3	L
PhyloP100		-0.041
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.67	N
REVEL	Benign	0.0090
Sift	Benign	0.63	T
Sift4G	Benign	0.31	T
Polyphen		0.016	B
Vest4		0.11
MutPred		0.25		Loss of glycosylation at S155 (P = 0.0833)
MVP		0.45
MPC		0.37
ClinPred		0.075	T
GERP RS		0.91
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.086
gMVP		0.16
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs776045935; hg19: chr2-10008475;