chr3-123284699-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_183357.3(ADCY5):c.3695C>T(p.Thr1232Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,240 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 (★★). Synonymous variant affecting the same amino acid position (i.e. T1232T) has been classified as Likely benign.
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.3695C>T | p.Thr1232Met | missense_variant | 21/21 | ENST00000462833.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY5 | ENST00000462833.6 | c.3695C>T | p.Thr1232Met | missense_variant | 21/21 | 1 | NM_183357.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152252Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000278 AC: 7AN: 251478Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135916
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461870Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727244
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152370Hom.: 0 Cov.: 33 AF XY: 0.0000268 AC XY: 2AN XY: 74518
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 29, 2023 | The c.3695C>T (p.T1232M) alteration is located in exon 21 (coding exon 21) of the ADCY5 gene. This alteration results from a C to T substitution at nucleotide position 3695, causing the threonine (T) at amino acid position 1232 to be replaced by a methionine (M). 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 | Dec 22, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1232 of the ADCY5 protein (p.Thr1232Met). This variant is present in population databases (rs201599722, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ADCY5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1900009). 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 with a negative predictive value of 95%. 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