dbSNP rs760680245: TFAP2E:p.Gly14Arg (chr1-35573939-G-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_178548.4(TFAP2E):c.40G>A(p.Gly14Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000766 in 1,305,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.7e-7 ( 0 hom. )

Consequence

TFAP2E
NM_178548.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.28

Publications

0 publications found

Variant links:

Genes affected

TFAP2E (HGNC:30774): (transcription factor AP-2 epsilon) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in anatomical structure development; regulation of cell population proliferation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TFAP2E links:

TFAP2E-AS1 (HGNC:41274): (TFAP2E antisense RNA 1)

TFAP2E-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40108544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178548.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFAP2E	NM_178548.4	MANE Select	c.40G>A	p.Gly14Arg	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
TFAP2E-AS1	NR_183383.1		n.880+421C>T		intron	N/A
TFAP2E-AS1	NR_183385.1		n.777+524C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFAP2E	ENST00000373235.4	TSL:1 MANE Select	c.40G>A	p.Gly14Arg	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+421C>T		intron	N/A
TFAP2E-AS1	ENST00000425881.1	TSL:3	n.-192C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000244

AC:

AN:

82112

AF XY:

0.0000212

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000221

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.66e-7

AC:

AN:

1305626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

643486

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25770

American (AMR)

AF:

0.00

AC:

AN:

20884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18846

East Asian (EAS)

AF:

0.00

AC:

AN:

31222

South Asian (SAS)

AF:

0.00

AC:

AN:

64918

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33032

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3646

European-Non Finnish (NFE)

AF:

9.49e-7

AC:

AN:

1053422

Other (OTH)

AF:

0.00

AC:

AN:

53886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.00000916

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

Pathogenic

0.60

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Uncertain

0.010

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

0.031

Eigen_PC

Benign

-0.043

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.98

MetaRNN

Benign

0.40

MetaSVM

Uncertain

0.72

MutationAssessor

Benign

1.8

PhyloP100

5.3

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.55

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.012

Polyphen

0.87

Vest4

0.39

MutPred

0.35

Gain of MoRF binding (P = 0.0279)

MVP

0.85

MPC

0.45

ClinPred

0.43

GERP RS

2.7

Varity_R

0.22

gMVP

0.55

Mutation Taster

=90/10

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