20-50891434-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_001282531.3(ADNP):c.3280G>A(p.Gly1094Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000435 in 1,610,510 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. G1094V) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADNP | NM_001282531.3 | c.3280G>A | p.Gly1094Arg | missense_variant | 6/6 | ENST00000621696.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADNP | ENST00000621696.5 | c.3280G>A | p.Gly1094Arg | missense_variant | 6/6 | 5 | NM_001282531.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000808 AC: 2AN: 247494Hom.: 0 AF XY: 0.00000747 AC XY: 1AN XY: 133818
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1458280Hom.: 0 Cov.: 35 AF XY: 0.00000276 AC XY: 2AN XY: 725434
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152230Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 24, 2023 | Variant summary: ADNP c.3280G>A (p.Gly1094Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 247494 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3280G>A in individuals affected with ADNP-Related Multiple Congenital Anomalies-Intellectual Disability-Autism Spectrum Disorder and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2023 | The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with ADNP-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1094 of the ADNP protein (p.Gly1094Arg). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at