16-84180078-C-G

Variant names:

• chr16-84180078-C-G
• rs4150167
• NM_001243156.2:c.1489G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001243156.2(TAF1C):​c.1489G>C​(p.Gly497Arg) 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. 14/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: TAF1C NM_001243156.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.542
• Publications: 0 publications found

Genes affected

TAF1C (HGNC:11534): (TATA-box binding protein associated factor, RNA polymerase I subunit C) 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 the largest SL1-specific TAF. Multiple alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2011]

TAF1C Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AR Classification: MODERATE Submitted by: PanelApp Australia
• complex neurodevelopmental disorder

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11645347).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243156.2. 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
	TAF1C	NM_001243156.2	MANE Select	c.1489G>C	p.Gly497Arg	missense	Exon 14 of 15	NP_001230085.2	Q15572-6
	TAF1C	NM_005679.4		c.1567G>C	p.Gly523Arg	missense	Exon 13 of 14	NP_005670.4
	TAF1C	NM_001243157.2		c.571G>C	p.Gly191Arg	missense	Exon 11 of 12	NP_001230086.1	Q15572-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1C	ENST00000566732.6	TSL:2 MANE Select	c.1489G>C	p.Gly497Arg	missense	Exon 14 of 15	ENSP00000455933.1	Q15572-6
	TAF1C	ENST00000341690.10	TSL:1	c.1285G>C	p.Gly429Arg	missense splice_region	Exon 14 of 15	ENSP00000345305.6	Q15572-2
	TAF1C	ENST00000567759.5	TSL:2	c.1567G>C	p.Gly523Arg	missense	Exon 13 of 14	ENSP00000455265.1	Q15572-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 75

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.015	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.54
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.043
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.030	D
Polyphen		0.98	D
Vest4		0.11
MutPred		0.31		Gain of solvent accessibility (P = 0.0014)
MVP		0.36
ClinPred		0.31	T
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.081
gMVP		0.54

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4150167; hg19: chr16-84213684;