chr1-222569621-GGT-CGG

Variant names:

• chr1-222569621-GGT-CGG
• NM_005681.4:c.781_783delACCinsCCG
• TAF1A p.Thr261Pro

Variant summary

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

The NM_005681.4(TAF1A):​c.781_783delACCinsCCG​(p.Thr261Pro) 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 Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TAF1A NM_005681.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.75
• Publications: 0 publications found

Genes affected

TAF1A (HGNC:11532): (TATA-box binding protein associated factor, RNA polymerase I subunit A) This gene encodes a subunit of the RNA polymerase I complex, Selectivity Factor I (SLI). The encoded protein is a TATA box-binding protein-associated factor that plays a role in the assembly of the RNA polymerase I preinitiation complex. Alternate splicing results in multiple transcript variants encoding multiple isoforms.[provided by RefSeq, Jan 2011]

TAF1A Gene-Disease associations (from GenCC):

• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005681.4. 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
	TAF1A	NM_005681.4	MANE Select	c.781_783delACCinsCCG	p.Thr261Pro	missense	N/A	NP_005672.1	Q15573-1
	TAF1A	NM_001201536.1		c.781_783delACCinsCCG	p.Thr261Pro	missense	N/A	NP_001188465.1	A8K4K5
	TAF1A	NM_139352.2		c.439_441delACCinsCCG	p.Thr147Pro	missense	N/A	NP_647603.1	Q15573-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TAF1A	ENST00000352967.9	TSL:1 MANE Select	c.781_783delACCinsCCG	p.Thr261Pro	missense	N/A	ENSP00000327072.6	Q15573-1
	TAF1A	ENST00000972077.1		c.916_918delACCinsCCG	p.Thr306Pro	missense	N/A	ENSP00000642136.1
	TAF1A	ENST00000350027.8	TSL:2	c.781_783delACCinsCCG	p.Thr261Pro	missense	N/A	ENSP00000339976.4	Q15573-1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

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: chr1-222742963;