GeneBe

rs1231511320

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_138422.4(ADAT3):​c.716A>C​(p.His239Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

ADAT3
NM_138422.4 missense

Scores

8
5
1

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

Publications

0 publications found
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 was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.922

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAT3NM_138422.4 linkc.716A>C p.His239Pro missense_variant Exon 2 of 2 ENST00000329478.4 NP_612431.2
SCAMP4NM_079834.4 linkc.-41-2216A>C intron_variant Intron 1 of 6 ENST00000316097.13 NP_524558.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAT3ENST00000329478.4 linkc.716A>C p.His239Pro missense_variant Exon 2 of 2 1 NM_138422.4 ENSP00000332448.2
SCAMP4ENST00000316097.13 linkc.-41-2216A>C intron_variant Intron 1 of 6 1 NM_079834.4 ENSP00000316007.7

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 16, 2016
Genetic Services Laboratory, University of Chicago
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.50
BayesDel_addAF
Pathogenic
0.37
D
BayesDel_noAF
Pathogenic
0.29
CADD
Uncertain
24
DANN
Uncertain
0.99
Eigen
Pathogenic
0.78
Eigen_PC
Uncertain
0.66
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Benign
0.71
T
M_CAP
Pathogenic
0.44
D
MetaRNN
Pathogenic
0.92
D
MetaSVM
Uncertain
0.39
D
PhyloP100
4.4
PrimateAI
Pathogenic
0.85
D
REVEL
Pathogenic
0.79
Sift4G
Pathogenic
0.0
D
Vest4
0.76
ClinPred
0.99
D
GERP RS
4.8
PromoterAI
0.012
Neutral
gMVP
0.88
Mutation Taster
=37/63
disease causing

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

Other links and lift over

dbSNP: rs1231511320; hg19: chr19-1912762; API