chr2-24821519-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PM2PP2PP3_Strong
The NM_004036.5(ADCY3):c.3125T>C(p.Ile1042Thr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_004036.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADCY3 | NM_004036.5 | c.3125T>C | p.Ile1042Thr | missense_variant, splice_region_variant | 20/22 | ENST00000679454.1 | |
CENPO | NM_001322101.2 | c.*2201A>G | 3_prime_UTR_variant | 8/8 | ENST00000380834.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADCY3 | ENST00000679454.1 | c.3125T>C | p.Ile1042Thr | missense_variant, splice_region_variant | 20/22 | NM_004036.5 | P4 | ||
CENPO | ENST00000380834.7 | c.*2201A>G | 3_prime_UTR_variant | 8/8 | 5 | NM_001322101.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251238Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135804
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1461662Hom.: 0 Cov.: 30 AF XY: 0.0000138 AC XY: 10AN XY: 727134
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
ADCY3-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 05, 2024 | The ADCY3 c.3128T>C variant is predicted to result in the amino acid substitution p.Ile1043Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0098% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at