6-50772791-A-C

Variant summary

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

The NM_172238.4(TFAP2D):​c.1286A>C​(p.Asn429Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

TFAP2D
NM_172238.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78
Variant links:
Genes affected
TFAP2D (HGNC:15581): (transcription factor AP-2 delta) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II transcription regulatory region sequence-specific 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 inferior colliculus development; negative regulation of neuron apoptotic process; and 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]

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=0.06737274).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
TFAP2DNM_172238.4 linkc.1286A>C p.Asn429Thr missense_variant 8/8 ENST00000008391.4 NP_758438.2 Q7Z6R9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TFAP2DENST00000008391.4 linkc.1286A>C p.Asn429Thr missense_variant 8/81 NM_172238.4 ENSP00000008391.4 Q7Z6R9

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 GeneticsFeb 13, 2024The c.1286A>C (p.N429T) alteration is located in exon 8 (coding exon 8) of the TFAP2D gene. This alteration results from a A to C substitution at nucleotide position 1286, causing the asparagine (N) at amino acid position 429 to be replaced by a threonine (T). 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
0.054
BayesDel_addAF
Benign
0.00045
T
BayesDel_noAF
Benign
-0.24
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.052
T
Eigen
Benign
-0.45
Eigen_PC
Benign
-0.26
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.65
T
M_CAP
Benign
0.049
D
MetaRNN
Benign
0.067
T
MetaSVM
Benign
-0.42
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.38
T
PROVEAN
Benign
-0.010
N
REVEL
Uncertain
0.35
Sift
Benign
0.51
T
Sift4G
Benign
0.49
T
Polyphen
0.010
B
Vest4
0.20
MutPred
0.10
Gain of phosphorylation at N429 (P = 0.0247);
MVP
0.068
MPC
0.38
ClinPred
0.33
T
GERP RS
1.7
Varity_R
0.087
gMVP
0.15

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: rs1024808673; hg19: chr6-50740504; API