Variant rs3734391 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372066.1(TFAP2A):c.1263C>T(p.Asn421=) variant causes a synonymous change. The variant allele was found at a frequency of 0.13 in 1,614,124 control chromosomes in the GnomAD database, including 14,464 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1192 hom., cov: 32)

Exomes 𝑓: 0.13 ( 13272 hom. )

Consequence

TFAP2A
NM_001372066.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 6.85

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 6-10398474-G-A is Benign according to our data. Variant chr6-10398474-G-A is described in ClinVar as [Benign]. Clinvar id is 258982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-10398474-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TFAP2A	NM_001372066.1 linkuse as main transcript	c.1263C>T	p.Asn421=	synonymous_variant	7/7	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3 linkuse as main transcript	c.1245C>T	p.Asn415=	synonymous_variant	7/7		NP_001035890.1
TFAP2A	NM_001032280.3 linkuse as main transcript	c.1239C>T	p.Asn413=	synonymous_variant	7/7		NP_001027451.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10 linkuse as main transcript	c.1263C>T	p.Asn421=	synonymous_variant	7/7	1	NM_001372066.1	ENSP00000368933	A1

Frequencies

GnomAD3 genomes

AF:

0.116

AC:

17683

AN:

152136

Hom.:

1192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0821

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.247

Gnomad EAS

AF:

0.0370

Gnomad SAS

AF:

0.103

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.140

Gnomad OTH

AF:

0.140

GnomAD3 exomes

AF:

0.116

AC:

29165

AN:

251072

Hom.:

1983

AF XY:

0.119

AC XY:

16180

AN XY:

135738

show subpopulations

Gnomad AFR exome

AF:

0.0842

Gnomad AMR exome

AF:

0.0731

Gnomad ASJ exome

AF:

0.237

Gnomad EAS exome

AF:

0.0220

Gnomad SAS exome

AF:

0.111

Gnomad FIN exome

AF:

0.0980

Gnomad NFE exome

AF:

0.142

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.132

AC:

192548

AN:

1461870

Hom.:

13272

Cov.:

AF XY:

0.132

AC XY:

96318

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.0820

Gnomad4 AMR exome

AF:

0.0771

Gnomad4 ASJ exome

AF:

0.237

Gnomad4 EAS exome

AF:

0.0609

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0998

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.133

GnomAD4 genome

AF:

0.116

AC:

17679

AN:

152254

Hom.:

1192

Cov.:

AF XY:

0.114

AC XY:

8461

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.0818

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.247

Gnomad4 EAS

AF:

0.0371

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.140

Gnomad4 OTH

AF:

0.138

Alfa

AF:

0.139

Hom.:

756

Bravo

AF:

0.115

Asia WGS

AF:

0.0610

AC:

213

AN:

3478

EpiCase

AF:

0.152

EpiControl

AF:

0.156

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 05, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.94

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over