3-123284645-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_183357.3(ADCY5):āc.3749T>Cā(p.Met1250Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000142 in 1,614,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M1250L) has been classified as Uncertain significance.
Frequency
Consequence
NM_183357.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY5 | NM_183357.3 | c.3749T>C | p.Met1250Thr | missense_variant | 21/21 | ENST00000462833.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY5 | ENST00000462833.6 | c.3749T>C | p.Met1250Thr | missense_variant | 21/21 | 1 | NM_183357.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152242Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251484Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461880Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727244
GnomAD4 genome AF: 0.000118 AC: 18AN: 152242Hom.: 0 Cov.: 33 AF XY: 0.000108 AC XY: 8AN XY: 74384
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 13, 2022 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ADCY5 protein function. ClinVar contains an entry for this variant (Variation ID: 1398651). This variant has not been reported in the literature in individuals affected with ADCY5-related conditions. This variant is present in population databases (rs142247122, gnomAD 0.02%). This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1250 of the ADCY5 protein (p.Met1250Thr). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at