Genetic Variant TFAP2A:c.770+36_770+37insCCGCCCCGCCCCGCCCCGC (chr6-10404471-C-CGCGGGGCGGGGCGGGGCGG) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_001372066.1(TFAP2A):c.770+36_770+37insCCGCCCCGCCCCGCCCCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000077 in 1,297,998 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, 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.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

TFAP2A
NM_001372066.1 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.19

Publications

0 publications found

Variant links:

Genes affected

TFAP2A (HGNC:11742): (transcription factor AP-2 alpha) The protein encoded by this gene is a transcription factor that binds the consensus sequence 5'-GCCNNNGGC-3'. The encoded protein functions as either a homodimer or as a heterodimer with similar family members. This protein activates the transcription of some genes while inhibiting the transcription of others. Defects in this gene are a cause of branchiooculofacial syndrome (BOFS). Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Dec 2009]

TFAP2A links:

TFAP2A-AS2 (HGNC:52289): (TFAP2A antisense RNA 2) The product of this intronless gene is a capped lncRNA that is nuclear-enriched and associated with chromatin. The encoded transcript may be involved in the regulation of developmental gene expression in a context-dependent manner, functioning as a repressor in non-pluripotent cells and an activator in pluripotent cells. Transcription of this gene is activated in 8-cell human embryos during the major wave of zygotic genome activation, independently of and prior to the activation of TFAP2A, an overlapping gene found on the opposite strand. Expression of this gene is characterized by high cell-to-cell variability in the cells of totipotent human embryos and in stable cell lines. [provided by RefSeq, Mar 2017]

TFAP2A-AS2 links:

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ACMG classification

Classification was made for transcript

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372066.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFAP2A	NM_001372066.1	MANE Select	c.770+36_770+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	NP_001358995.1	A0A6E1XE14
TFAP2A	NM_001042425.3		c.752+36_752+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	NP_001035890.1	P05549-6
TFAP2A	NM_001032280.3		c.746+36_746+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	NP_001027451.1	P05549-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.770+36_770+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	ENSP00000368933.5	A0A6E1XE14
TFAP2A	ENST00000379608.9	TSL:1	c.746+36_746+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	ENSP00000368928.3	P05549-5
TFAP2A	ENST00000466073.5	TSL:1	c.764+36_764+37insCCGCCCCGCCCCGCCCCGC	intron	N/A	ENSP00000417495.1	C1K3N0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.70e-7

AC:

AN:

1297998

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

637208

show subpopulations

African (AFR)

AF:

0.0000377

AC:

AN:

26512

American (AMR)

AF:

0.00

AC:

AN:

25844

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21492

East Asian (EAS)

AF:

0.00

AC:

AN:

29994

South Asian (SAS)

AF:

0.00

AC:

AN:

66810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43976

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4448

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1025686

Other (OTH)

AF:

0.00

AC:

AN:

53236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Splicing

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

Publications

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6-10404471-CGCGGG-CGCGGGGCGGGGCGGGGCGGGCGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over