1-35573996-GGG-CGC

Variant names:

• chr1-35573996-GGG-CGC
• NM_178548.4:c.97_99delGGGinsCGC
• TFAP2E p.Gly33Arg

Variant summary

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

The NM_178548.4(TFAP2E):​c.97_99delGGGinsCGC​(p.Gly33Arg) 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33E) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TFAP2E NM_178548.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.118
• Publications: 0 publications found

Genes affected

TFAP2E (HGNC:30774): (transcription factor AP-2 epsilon) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in anatomical structure development; regulation of cell population proliferation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TFAP2E-AS1 (HGNC:41274): (TFAP2E antisense RNA 1)

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178548.4. 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
	TFAP2E	NM_178548.4	MANE Select	c.97_99delGGGinsCGC	p.Gly33Arg	missense	N/A	NP_848643.2	Q6VUC0
	TFAP2E-AS1	NR_183383.1		n.880+362_880+364delCCCinsGCG		intron	N/A
	TFAP2E-AS1	NR_183385.1		n.777+465_777+467delCCCinsGCG		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2E	ENST00000373235.4	TSL:1 MANE Select	c.97_99delGGGinsCGC	p.Gly33Arg	missense	N/A	ENSP00000362332.3	Q6VUC0
	TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+362_826+364delCCCinsGCG		intron	N/A
	TFAP2E-AS1	ENST00000425881.1	TSL:3	n.-251_-249delCCCinsGCG		upstream_gene	N/A

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		0.12

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: chr1-36039597;