chr19-1912205-CAG-C
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Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PVS1_StrongPM2PP5_Moderate
The NM_138422.4(ADAT3):βc.159_160delβ(p.Asp55ArgfsTer69) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000692 in 1,589,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (β ).
Frequency
Genomes: π 0.000013 ( 0 hom., cov: 33)
Exomes π: 0.0000063 ( 0 hom. )
Consequence
ADAT3
NM_138422.4 frameshift
NM_138422.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.0470
Genes affected
ADAT3 (HGNC:25151): (adenosine deaminase tRNA specific 3) This gene encodes a subunit of a tRNA-specific adenosine deaminase. This heterodimeric enzyme converts adenosine to inosine in the tRNA anticodon. A mutation in this gene causes a syndrome characterized by intellectual disability and strabismus. This gene shares its 5' exon with the overlapping gene, secretory carrier membrane protein 4 (Gene ID: 113178). [provided by RefSeq, Jul 2016]
SCAMP4 (HGNC:30385): (secretory carrier membrane protein 4) Secretory carrier membrane proteins (SCAMPs) are widely distributed integral membrane proteins implicated in membrane trafficking. Most SCAMPs (e.g., SCAMP1; MIM 606911) have N-terminal cytoplasmic NPF (arg-pro-phe) repeats, 4 central transmembrane regions, and a short C-terminal cytoplasmic tail. These SCAMPs likely have a role in endocytosis that is mediated by their NPF repeats. Other SCAMPs, such as SCAMP4, lack the NPF repeats and are therefore unlikely to function in endocytosis (summary by Fernandez-Chacon and Sudhof, 2000 [PubMed 11050114]).[supplied by OMIM, Feb 2011]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.856 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 19-1912205-CAG-C is Pathogenic according to our data. Variant chr19-1912205-CAG-C is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3362604.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ADAT3 | NM_138422.4 | c.159_160del | p.Asp55ArgfsTer69 | frameshift_variant | 2/2 | ENST00000329478.4 | NP_612431.2 | |
SCAMP4 | NM_079834.4 | c.-41-2773_-41-2772del | intron_variant | ENST00000316097.13 | NP_524558.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ADAT3 | ENST00000329478.4 | c.159_160del | p.Asp55ArgfsTer69 | frameshift_variant | 2/2 | 1 | NM_138422.4 | ENSP00000332448 | P1 | |
SCAMP4 | ENST00000316097.13 | c.-41-2773_-41-2772del | intron_variant | 1 | NM_079834.4 | ENSP00000316007 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000100 AC: 2AN: 199894Hom.: 0 AF XY: 0.0000182 AC XY: 2AN XY: 109844
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GnomAD4 exome AF: 0.00000626 AC: 9AN: 1437542Hom.: 0 AF XY: 0.00000701 AC XY: 5AN XY: 713692
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GnomAD4 genome AF: 0.0000131 AC: 2AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74382
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Intellectual disability-strabismus syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center | Sep 22, 2024 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at