19-1912298-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_138422.4(ADAT3):c.251C>G(p.Pro84Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000243 in 1,564,890 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00026 ( 0 hom. )
Consequence
ADAT3
NM_138422.4 missense
NM_138422.4 missense
Scores
1
6
7
Clinical Significance
Conservation
PhyloP100: 4.08
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAT3 | NM_138422.4 | c.251C>G | p.Pro84Arg | missense_variant | 2/2 | ENST00000329478.4 | |
SCAMP4 | NM_079834.4 | c.-41-2681C>G | intron_variant | ENST00000316097.13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAT3 | ENST00000329478.4 | c.251C>G | p.Pro84Arg | missense_variant | 2/2 | 1 | NM_138422.4 | P1 | |
SCAMP4 | ENST00000316097.13 | c.-41-2681C>G | intron_variant | 1 | NM_079834.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152240Hom.: 0 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.000125 AC: 20AN: 160438Hom.: 0 AF XY: 0.000111 AC XY: 10AN XY: 89696
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GnomAD4 exome AF: 0.000258 AC: 364AN: 1412650Hom.: 0 Cov.: 30 AF XY: 0.000258 AC XY: 181AN XY: 700264
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GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152240Hom.: 0 Cov.: 33 AF XY: 0.0000941 AC XY: 7AN XY: 74370
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 16, 2021 | The c.203C>G (p.P68R) alteration is located in exon 2 (coding exon 1) of the ADAT3 gene. This alteration results from a C to G substitution at nucleotide position 203, causing the proline (P) at amino acid position 68 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Benign
D
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
REVEL
Uncertain
Sift4G
Uncertain
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at