Genetic Variant TFAP2C:p.Ala162Val (chr20-56631641-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003222.4(TFAP2C):c.485C>T(p.Ala162Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000298 in 1,579,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

TFAP2C
NM_003222.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.222

Publications

0 publications found

Variant links:

Genes affected

TFAP2C (HGNC:11744): (transcription factor AP-2 gamma) The protein encoded by this gene is a sequence-specific DNA-binding transcription factor involved in the activation of several developmental genes. The encoded protein can act as either a homodimer or heterodimer with other family members and is induced during retinoic acid-mediated differentiation. It plays a role in the development of the eyes, face, body wall, limbs, and neural tube. [provided by RefSeq, Jul 2008]

TFAP2C links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10846126).

BS2

High AC in GnomAdExome4 at 44 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003222.4. 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
	TFAP2C	NM_003222.4	MANE Select	c.485C>T	p.Ala162Val	missense	Exon 2 of 7	NP_003213.1	Q92754-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFAP2C	ENST00000201031.3	TSL:1 MANE Select	c.485C>T	p.Ala162Val	missense	Exon 2 of 7	ENSP00000201031.2	Q92754-1
TFAP2C	ENST00000882953.1		c.485C>T	p.Ala162Val	missense	Exon 2 of 7	ENSP00000553012.1
TFAP2C	ENST00000416606.1	TSL:3	c.*94C>T		downstream_gene	N/A	ENSP00000390857.1	A2A2R7

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000987

AC:

AN:

202588

AF XY:

0.00000893

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000800

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000308

AC:

AN:

1426900

Hom.:

Cov.:

AF XY:

0.0000297

AC XY:

AN XY:

708146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32520

American (AMR)

AF:

0.00

AC:

AN:

41710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25020

East Asian (EAS)

AF:

0.00

AC:

AN:

38530

South Asian (SAS)

AF:

0.00

AC:

AN:

81844

European-Finnish (FIN)

AF:

0.0000238

AC:

AN:

42054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5682

European-Non Finnish (NFE)

AF:

0.0000354

AC:

AN:

1100354

Other (OTH)

AF:

0.0000676

AC:

AN:

59186

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000197

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000828

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.49

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.41

LIST_S2

Uncertain

0.93

M_CAP

Uncertain

0.087

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.7

PhyloP100

0.22

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

REVEL

Benign

0.12

Sift

Benign

0.092

Sift4G

Benign

0.24

Polyphen

0.012

Vest4

0.16

MVP

0.53

MPC

0.90

ClinPred

0.19

GERP RS

3.4

Varity_R

0.10

gMVP

0.30

Mutation Taster

=84/16

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over