1-35574381-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178548.4(TFAP2E):​c.482C>T​(p.Ala161Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000543 in 1,435,534 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

TFAP2E
NM_178548.4 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.09
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-AS1 (HGNC:41274): (TFAP2E antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.04602009).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TFAP2ENM_178548.4 linkuse as main transcriptc.482C>T p.Ala161Val missense_variant 2/7 ENST00000373235.4 NP_848643.2
TFAP2E-AS1NR_183386.1 linkuse as main transcriptn.504+2978G>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TFAP2EENST00000373235.4 linkuse as main transcriptc.482C>T p.Ala161Val missense_variant 2/71 NM_178548.4 ENSP00000362332 P1
TFAP2E-AS1ENST00000444348.3 linkuse as main transcriptn.776G>A non_coding_transcript_exon_variant 2/33

Frequencies

GnomAD3 genomes
AF:
0.0000789
AC:
12
AN:
152098
Hom.:
0
Cov.:
33
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:
0.0000944
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000156
AC:
7
AN:
44802
Hom.:
0
AF XY:
0.000117
AC XY:
3
AN XY:
25742
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000145
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000350
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000243
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000514
AC:
66
AN:
1283436
Hom.:
0
Cov.:
30
AF XY:
0.0000493
AC XY:
31
AN XY:
629144
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000579
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000607
Gnomad4 OTH exome
AF:
0.0000376
GnomAD4 genome
AF:
0.0000789
AC:
12
AN:
152098
Hom.:
0
Cov.:
33
AF XY:
0.0000942
AC XY:
7
AN XY:
74300
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000944
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000162
Hom.:
0
Bravo
AF:
0.0000491
ExAC
AF:
0.0000423
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsJul 13, 2021The c.482C>T (p.A161V) alteration is located in exon 2 (coding exon 2) of the TFAP2E gene. This alteration results from a C to T substitution at nucleotide position 482, causing the alanine (A) at amino acid position 161 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.059
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.28
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.59
T
M_CAP
Benign
0.068
D
MetaRNN
Benign
0.046
T
MetaSVM
Benign
-0.53
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.72
N
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.18
Sift
Benign
0.035
D
Sift4G
Benign
0.16
T
Polyphen
0.25
B
Vest4
0.42
MVP
0.78
MPC
0.68
ClinPred
0.083
T
GERP RS
4.3
Varity_R
0.11
gMVP
0.22

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.

Other links and lift over

dbSNP: rs573787324; hg19: chr1-36039982; API