19-1912252-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_138422.4(ADAT3):​c.205A>C​(p.Lys69Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)

Consequence

ADAT3
NM_138422.4 missense

Scores

4
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.01
Variant links:
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.29699707).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAT3NM_138422.4 linkuse as main transcriptc.205A>C p.Lys69Gln missense_variant 2/2 ENST00000329478.4 NP_612431.2
SCAMP4NM_079834.4 linkuse as main transcriptc.-41-2727A>C intron_variant ENST00000316097.13 NP_524558.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAT3ENST00000329478.4 linkuse as main transcriptc.205A>C p.Lys69Gln missense_variant 2/21 NM_138422.4 ENSP00000332448 P1
SCAMP4ENST00000316097.13 linkuse as main transcriptc.-41-2727A>C intron_variant 1 NM_079834.4 ENSP00000316007 P1Q969E2-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
34

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 submitterclinical testingAmbry GeneticsJun 17, 2024The c.157A>C (p.K53Q) alteration is located in exon 2 (coding exon 1) of the ADAT3 gene. This alteration results from a A to C substitution at nucleotide position 157, causing the lysine (K) at amino acid position 53 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.11
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
20
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
.;T
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.10
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.60
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.51
T
REVEL
Benign
0.28
Sift4G
Benign
0.13
T;D
Vest4
0.14
MVP
0.49
MPC
0.64
ClinPred
0.50
T
GERP RS
3.8
gMVP
0.49

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-1912251; API