dbSNP rs3734391: TFAP2A:p.Asn421Asn (chr6-10398474-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001372066.1(TFAP2A):c.1263C>T(p.Asn421Asn) 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

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

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

TFAP2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 258982.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TFAP2A	NM_001372066.1 link	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 7 of 7	ENST00000379613.10	NP_001358995.1
TFAP2A	NM_001042425.3 link	c.1245C>T	p.Asn415Asn	synonymous_variant	Exon 7 of 7		NP_001035890.1	P05549-6
TFAP2A	NM_001032280.3 link	c.1239C>T	p.Asn413Asn	synonymous_variant	Exon 7 of 7		NP_001027451.1	P05549-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TFAP2A	ENST00000379613.10 link	c.1263C>T	p.Asn421Asn	synonymous_variant	Exon 7 of 7	1	NM_001372066.1	ENSP00000368933.5		A0A6E1XE14

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

GnomAD2 exomes

AF:

0.116

AC:

29165

AN:

251072

AF XY:

0.119

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 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

African (AFR)

AF:

0.0820

AC:

2744

AN:

33480

American (AMR)

AF:

0.0771

AC:

3449

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.237

AC:

6195

AN:

26136

East Asian (EAS)

AF:

0.0609

AC:

2417

AN:

39700

South Asian (SAS)

AF:

0.114

AC:

9835

AN:

86258

European-Finnish (FIN)

AF:

0.0998

AC:

5330

AN:

53420

Middle Eastern (MID)

AF:

0.174

AC:

1002

AN:

5768

European-Non Finnish (NFE)

AF:

0.138

AC:

153533

AN:

1111992

Other (OTH)

AF:

0.133

AC:

8043

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

11209

22419

33628

44838

56047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5388

10776

16164

21552

26940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.116

AC:

17679

AN:

152254

Hom.:

1192

Cov.:

AF XY:

0.114

AC XY:

8461

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0818

AC:

3397

AN:

41550

American (AMR)

AF:

0.109

AC:

1669

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.247

AC:

856

AN:

3470

East Asian (EAS)

AF:

0.0371

AC:

192

AN:

5180

South Asian (SAS)

AF:

0.104

AC:

500

AN:

4820

European-Finnish (FIN)

AF:

0.101

AC:

1074

AN:

10614

Middle Eastern (MID)

AF:

0.221

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.140

AC:

9534

AN:

67996

Other (OTH)

AF:

0.138

AC:

292

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

758

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

Sep 05, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

6.8

Mutation Taster

=77/23

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over