Genetic Variant TFAP2E:p.Gly33Trp (chr1-35573996-G-T) – 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.97G>T(p.Gly33Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000752 in 1,330,332 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G33E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

TFAP2E
NM_178548.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.781

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:

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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=0.40506232).

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.97G>T	p.Gly33Trp	missense	Exon 2 of 7	NP_848643.2	Q6VUC0
TFAP2E-AS1	NR_183383.1		n.880+364C>A		intron	N/A
TFAP2E-AS1	NR_183385.1		n.777+467C>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TFAP2E	ENST00000373235.4	TSL:1 MANE Select	c.97G>T	p.Gly33Trp	missense	Exon 2 of 7	ENSP00000362332.3	Q6VUC0
TFAP2E-AS1	ENST00000444348.4	TSL:3	n.826+364C>A		intron	N/A
TFAP2E-AS1	ENST00000425881.1	TSL:3	n.-249C>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.52e-7

AC:

AN:

1330332

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

656968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26622

American (AMR)

AF:

0.00

AC:

AN:

27292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22782

East Asian (EAS)

AF:

0.00

AC:

AN:

29788

South Asian (SAS)

AF:

0.00

AC:

AN:

73686

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33230

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3884

European-Non Finnish (NFE)

AF:

9.45e-7

AC:

AN:

1057982

Other (OTH)

AF:

0.00

AC:

AN:

55066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.57

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.34

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.16

LIST_S2

Uncertain

0.97

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.1

PhyloP100

-0.78

PrimateAI

Pathogenic

0.94

PROVEAN

Uncertain

-2.7

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0040

Polyphen

0.72

Vest4

0.46

MutPred

0.26

Loss of disorder (P = 0.0436)

MVP

0.47

MPC

1.2

ClinPred

0.95

GERP RS

0.36

Varity_R

0.30

gMVP

0.44

Mutation Taster

=89/11

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

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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