2-9882734-A-G

Variant names:

• chr2-9882734-A-G
• NM_005680.3:c.736A>G

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.736A>G​(p.Ile246Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 6.9e-7 (0 hom.)
• Consequence: TAF1B NM_005680.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.508
• 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=0.06719512).

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.736A>G	p.Ile246Val	missense	Exon 8 of 15	NP_005671.3	Q53T94-1
	TAF1B	NM_001318976.1		c.-30A>G		5_prime_UTR	Exon 8 of 15	NP_001305905.1	Q53T94
	TAF1B	NM_001318977.1		c.-30A>G		5_prime_UTR	Exon 7 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.736A>G	p.Ile246Val	missense	Exon 8 of 15	ENSP00000263663.4	Q53T94-1
	TAF1B	ENST00000944452.1		c.832A>G	p.Ile278Val	missense	Exon 9 of 16	ENSP00000614511.1
	TAF1B	ENST00000492648.2	TSL:5	c.49A>G	p.Ile17Val	missense	Exon 2 of 6	ENSP00000475608.1	U3KQ75

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459244 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 725848

African (AFR) AF: 0.00 AC: 0 AN: 33398

American (AMR) AF: 0.00 AC: 0 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.00 AC: 0 AN: 85600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1110854

Other (OTH) AF: 0.00 AC: 0 AN: 60262

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	12
DANN	Benign	0.79
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.55
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.42	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.96	L
PhyloP100		0.51
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.021
Sift	Benign	0.087	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.39		Gain of catalytic residue at I246 (P = 0.0495)
MVP		0.21
MPC		0.093
ClinPred		0.091	T
GERP RS		2.1
Varity_R		0.017
gMVP		0.18
Mutation Taster		=91/9	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

hg19: chr2-10022863;