chr4-41745938-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1PM2BP4
The NM_003924.4(PHOX2B):c.814G>A(p.Gly272Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000127 in 1,575,008 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G272D) has been classified as Uncertain significance.
Frequency
Consequence
NM_003924.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PHOX2B | NM_003924.4 | c.814G>A | p.Gly272Ser | missense_variant | 3/3 | ENST00000226382.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PHOX2B | ENST00000226382.4 | c.814G>A | p.Gly272Ser | missense_variant | 3/3 | 1 | NM_003924.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000663 AC: 1AN: 150866Hom.: 0 Cov.: 32
GnomAD4 exome AF: 7.02e-7 AC: 1AN: 1424142Hom.: 0 Cov.: 31 AF XY: 0.00000141 AC XY: 1AN XY: 708204
GnomAD4 genome AF: 0.00000663 AC: 1AN: 150866Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1AN XY: 73622
ClinVar
Submissions by phenotype
Haddad syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2023 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 467750). This variant has not been reported in the literature in individuals affected with PHOX2B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 272 of the PHOX2B protein (p.Gly272Ser). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 14, 2023 | The p.G272S variant (also known as c.814G>A), located in coding exon 3 of the PHOX2B gene, results from a G to A substitution at nucleotide position 814. The glycine at codon 272 is replaced by serine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at