chr19-1912063-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_138422.4(ADAT3):​c.16C>T​(p.Arg6Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000234 in 1,282,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 34)
Exomes 𝑓: 0.0000023 ( 0 hom. )

Consequence

ADAT3
NM_138422.4 missense

Scores

11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.362
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.14604992).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAT3NM_138422.4 linkuse as main transcriptc.16C>T p.Arg6Cys missense_variant 2/2 ENST00000329478.4 NP_612431.2
SCAMP4NM_079834.4 linkuse as main transcriptc.-41-2916C>T 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.16C>T p.Arg6Cys missense_variant 2/21 NM_138422.4 ENSP00000332448 P1
SCAMP4ENST00000316097.13 linkuse as main transcriptc.-41-2916C>T intron_variant 1 NM_079834.4 ENSP00000316007 P1Q969E2-1

Frequencies

GnomAD3 genomes
Cov.:
34
GnomAD4 exome
AF:
0.00000234
AC:
3
AN:
1282964
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
625020
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000291
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
34
ExAC
AF:
0.0000118
AC:
1

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Nov 30, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
16
DANN
Benign
0.92
DEOGEN2
Benign
0.012
.;T
FATHMM_MKL
Benign
0.081
N
LIST_S2
Benign
0.52
T;T
M_CAP
Benign
0.0040
T
MetaRNN
Benign
0.15
T;T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.35
T
Sift4G
Benign
0.082
T;T
Vest4
0.20
MVP
0.58
MPC
0.54
GERP RS
-7.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.3
gMVP
0.30

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs770766635; hg19: chr19-1912062; API