chr20-50891433-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001282531.3(ADNP):c.3281G>T(p.Gly1094Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000343 in 1,458,320 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G1094R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001282531.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADNP | NM_001282531.3 | c.3281G>T | p.Gly1094Val | missense_variant | 6/6 | ENST00000621696.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADNP | ENST00000621696.5 | c.3281G>T | p.Gly1094Val | missense_variant | 6/6 | 5 | NM_001282531.3 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000404 AC: 1AN: 247626Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133894
GnomAD4 exome AF: 0.00000343 AC: 5AN: 1458320Hom.: 0 Cov.: 35 AF XY: 0.00000414 AC XY: 3AN XY: 725474
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 16, 2022 | The c.3281G>T (p.G1094V) alteration is located in exon 5 (coding exon 3) of the ADNP gene. This alteration results from a G to T substitution at nucleotide position 3281, causing the glycine (G) at amino acid position 1094 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1094 of the ADNP protein (p.Gly1094Val). This variant is present in population databases (rs780706686, gnomAD 0.003%). This missense change has been observed in individual(s) with autism spectrum disorder (PMID: 26637798). 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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