6-10398329-G-T

Position:

• chr6-10398329-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001372066.1(TFAP2A):​c.*88C>A variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.05 in 1,606,400 control chromosomes in the GnomAD database, including 2,511 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.033 (133 hom., cov: 29)
  • Exomes 𝑓: 0.052 (2378 hom.)
• Consequence: TFAP2A NM_001372066.1 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 6.43

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-10398329-G-T is Benign according to our data. Variant chr6-10398329-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1203480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TFAP2A	NM_001372066.1	c.*88C>A		3_prime_UTR_variant	7/7	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3	c.*88C>A		3_prime_UTR_variant	7/7		NP_001035890.1
TFAP2A	NM_001032280.3	c.*88C>A		3_prime_UTR_variant	7/7		NP_001027451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613	c.*88C>A		3_prime_UTR_variant	7/7	1	NM_001372066.1	ENSP00000368933.5

Frequencies

GnomAD3 genomes AF: 0.0327 AC: 4918 AN: 150602 Hom.: 133 Cov.: 29

Gnomad AFR AF: 0.0111

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.0231

Gnomad ASJ AF: 0.0156

Gnomad EAS AF: 0.000394

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0542

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.0518 AC: 75447 AN: 1455684 Hom.: 2378 Cov.: 36 AF XY: 0.0505 AC XY: 36552 AN XY: 723932

Gnomad4 AFR exome AF: 0.00836

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0178

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0157

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0619

Gnomad4 OTH exome AF: 0.0452

GnomAD4 genome AF: 0.0326 AC: 4918 AN: 150716 Hom.: 133 Cov.: 29 AF XY: 0.0308 AC XY: 2262 AN XY: 73554

Gnomad4 AFR AF: 0.0111

Gnomad4 AMR AF: 0.0230

Gnomad4 ASJ AF: 0.0156

Gnomad4 EAS AF: 0.000593

Gnomad4 SAS AF: 0.0124

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0542

Gnomad4 OTH AF: 0.0284

Alfa AF: 0.0146 Hom.: 2

Bravo AF: 0.0313

Asia WGS AF: 0.00722 AC: 25 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.88

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

Publications

LitVar

Other links and lift over

dbSNP: rs10456013; hg19: chr6-10398562;