chr6-10398448-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001372066.1(TFAP2A):c.1289G>A(p.Ser430Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000105 in 1,614,074 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
Consequence
NM_001372066.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TFAP2A | NM_001372066.1 | c.1289G>A | p.Ser430Asn | missense_variant | Exon 7 of 7 | ENST00000379613.10 | NP_001358995.1 | |
TFAP2A | NM_001042425.3 | c.1271G>A | p.Ser424Asn | missense_variant | Exon 7 of 7 | NP_001035890.1 | ||
TFAP2A | NM_001032280.3 | c.1265G>A | p.Ser422Asn | missense_variant | Exon 7 of 7 | NP_001027451.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TFAP2A | ENST00000379613.10 | c.1289G>A | p.Ser430Asn | missense_variant | Exon 7 of 7 | 1 | NM_001372066.1 | ENSP00000368933.5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250330Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135340
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461892Hom.: 0 Cov.: 38 AF XY: 0.00000963 AC XY: 7AN XY: 727246
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152182Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74330
ClinVar
Submissions by phenotype
not provided Uncertain:2
ClinVar contains an entry for this variant (Variation ID: 1202377). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 428 of the TFAP2A protein (p.Ser428Asn). This variant is present in population databases (rs778294642, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with TFAP2A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at