16-84180076-CCC-TCG

Variant names:

• chr16-84180076-CCC-TCG
• NM_001243156.2:c.1489_1491delGGGinsCGA
• TAF1C p.Gly497Arg

Variant summary

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

The NM_001243156.2(TAF1C):​c.1489_1491delGGGinsCGA​(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. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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.

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.1489_1491delGGGinsCGA	p.Gly497Arg	missense	N/A	NP_001230085.2	Q15572-6
	TAF1C	NM_005679.4		c.1567_1569delGGGinsCGA	p.Gly523Arg	missense	N/A	NP_005670.4
	TAF1C	NM_001243157.2		c.571_573delGGGinsCGA	p.Gly191Arg	missense	N/A	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.1489_1491delGGGinsCGA	p.Gly497Arg	missense	N/A	ENSP00000455933.1	Q15572-6
	TAF1C	ENST00000341690.10	TSL:1	c.1285_1287delGGGinsCGA	p.Gly429Arg	missense splice_region	N/A	ENSP00000345305.6	Q15572-2
	TAF1C	ENST00000567759.5	TSL:2	c.1567_1569delGGGinsCGA	p.Gly523Arg	missense	N/A	ENSP00000455265.1	Q15572-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.54

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-84213682;