chr6-50823486-C-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003221.4(TFAP2B):c.161C>G(p.Ala54Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,034 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003221.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TFAP2B | ENST00000393655.4 | c.161C>G | p.Ala54Gly | missense_variant | Exon 2 of 7 | 1 | NM_003221.4 | ENSP00000377265.2 | ||
TFAP2B | ENST00000344788.7 | c.155C>G | p.Ala52Gly | missense_variant | Exon 3 of 4 | 3 | ENSP00000342252.3 | |||
TFAP2B | ENST00000489228.1 | n.456C>G | non_coding_transcript_exon_variant | Exon 2 of 2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152044Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246284Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133382
GnomAD4 exome AF: 0.0000110 AC: 16AN: 1460990Hom.: 0 Cov.: 33 AF XY: 0.0000151 AC XY: 11AN XY: 726730
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152044Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74262
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.161C>G (p.A54G) alteration is located in exon 2 (coding exon 2) of the TFAP2B gene. This alteration results from a C to G substitution at nucleotide position 161, causing the alanine (A) at amino acid position 54 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 54 of the TFAP2B protein (p.Ala54Gly). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with TFAP2B-related conditions. ClinVar contains an entry for this variant (Variation ID: 1418292). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TFAP2B protein function with a negative predictive value of 80%. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at