ENST00000379608.9:c.-359A>T

Variant names:

• chr6-10411955-T-A
• rs1675414
• ENST00000379608.9:c.-359A>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000379608.9(TFAP2A):​c.-359A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TFAP2A ENST00000379608.9 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.866
• Publications: 18 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-AS1 (HGNC:40579): (TFAP2A antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379608.9. 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.52-1620A>T		intron	N/A	NP_001358995.1
	TFAP2A	NM_001032280.3		c.-359A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_001027451.1
	TFAP2A	NM_001032280.3		c.-359A>T		5_prime_UTR	Exon 1 of 7	NP_001027451.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TFAP2A	ENST00000379608.9	TSL:1	c.-359A>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000368928.3
	TFAP2A	ENST00000379608.9	TSL:1	c.-359A>T		5_prime_UTR	Exon 1 of 7	ENSP00000368928.3
	TFAP2A	ENST00000379613.10	TSL:1 MANE Select	c.52-1620A>T		intron	N/A	ENSP00000368933.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 947810 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 445258

African (AFR) AF: 0.00 AC: 0 AN: 18540

American (AMR) AF: 0.00 AC: 0 AN: 6382

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8058

East Asian (EAS) AF: 0.00 AC: 0 AN: 9906

South Asian (SAS) AF: 0.00 AC: 0 AN: 30652

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2066

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 833410

Other (OTH) AF: 0.00 AC: 0 AN: 33652

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	18
DANN	Benign	0.85
PhyloP100		0.87
PromoterAI		-0.049	Neutral

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: rs1675414; hg19: chr6-10412188;