6-10398329-G-C

Variant names:

• chr6-10398329-G-C
• rs10456013
• ENST00000488193.7:n.*899C>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000488193.7(TFAP2A):​n.*899C>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000685 in 1,606,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: TFAP2A ENST00000488193.7 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.43
• Publications: 3 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 Gene-Disease associations (from GenCC):

• branchiooculofacial syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000488193.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	NM_001372066.1	MANE Select	c.*88C>G		3_prime_UTR	Exon 7 of 7	NP_001358995.1
	TFAP2A	NM_001042425.3		c.*88C>G		3_prime_UTR	Exon 7 of 7	NP_001035890.1
	TFAP2A	NM_001032280.3		c.*88C>G		3_prime_UTR	Exon 7 of 7	NP_001027451.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000488193.7	TSL:1	n.*899C>G		non_coding_transcript_exon	Exon 8 of 8	ENSP00000419823.3
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.*88C>G		3_prime_UTR	Exon 7 of 7	ENSP00000368933.5
	TFAP2A	ENST00000379608.9	TSL:1	c.*88C>G		3_prime_UTR	Exon 7 of 7	ENSP00000368928.3

Frequencies

GnomAD3 genomes AF: 0.00000664 AC: 1 AN: 150624 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000687 AC: 10 AN: 1455766 Hom.: 0 Cov.: 36 AF XY: 0.00000691 AC XY: 5 AN XY: 723974

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.000134 AC: 6 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25956

East Asian (EAS) AF: 0.00 AC: 0 AN: 39646

South Asian (SAS) AF: 0.00 AC: 0 AN: 85902

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51856

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4458

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1109876

Other (OTH) AF: 0.00 AC: 0 AN: 60050

GnomAD4 genome AF: 0.00000664 AC: 1 AN: 150624 Hom.: 0 Cov.: 29 AF XY: 0.0000136 AC XY: 1 AN XY: 73438

African (AFR) AF: 0.00 AC: 0 AN: 40842

American (AMR) AF: 0.00 AC: 0 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.00 AC: 0 AN: 4766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10362

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67750

Other (OTH) AF: 0.00 AC: 0 AN: 2056

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		6.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs10456013; hg19: chr6-10398562;