rs564179777

Variant names:

• chr6-10404471-CGCGGG-C
• rs564179777
• NM_001372066.1:c.770+32_770+36delCCCGC

Your query was ambiguous. Multiple possible variants found:

• chr6-10404471-CGCGGG-C
• chr6-10404471-CGCGGG-CGCGGGGCGGG
• chr6-10404471-CGCGGG-CGCGGGGCGGGGCGGGGCGGGCGGG
• chr6-10404471-CGCGGG-CGCGGGGCGGGGCGGG

Variant summary

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

The NM_001372066.1(TFAP2A):​c.770+32_770+36delCCCGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000154 in 1,297,960 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: TFAP2A NM_001372066.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.19
• Publications: 0 publications found

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-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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	NM_001372066.1	MANE Select	c.770+32_770+36delCCCGC		intron	N/A	NP_001358995.1	A0A6E1XE14
	TFAP2A	NM_001042425.3		c.752+32_752+36delCCCGC		intron	N/A	NP_001035890.1	P05549-6
	TFAP2A	NM_001032280.3		c.746+32_746+36delCCCGC		intron	N/A	NP_001027451.1	P05549-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.770+32_770+36delCCCGC		intron	N/A	ENSP00000368933.5	A0A6E1XE14
	TFAP2A	ENST00000379608.9	TSL:1	c.746+32_746+36delCCCGC		intron	N/A	ENSP00000368928.3	P05549-5
	TFAP2A	ENST00000466073.5	TSL:1	c.764+32_764+36delCCCGC		intron	N/A	ENSP00000417495.1	C1K3N0

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000106 AC: 1 AN: 94340 AF XY: 0.0000189

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000276

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000154 AC: 2 AN: 1297960 Hom.: 0 AF XY: 0.00000157 AC XY: 1 AN XY: 637188

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000377 AC: 1 AN: 26512

American (AMR) AF: 0.00 AC: 0 AN: 25844

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21490

East Asian (EAS) AF: 0.00 AC: 0 AN: 29994

South Asian (SAS) AF: 0.0000150 AC: 1 AN: 66802

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4448

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1025660

Other (OTH) AF: 0.00 AC: 0 AN: 53236

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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

Other links and lift over

dbSNP: rs564179777; hg19: chr6-10404704;