chr19-1912103-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.56C>T​(p.Pro19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,508,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

ADAT3
NM_138422.4 missense

Scores

1
2
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.15
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=0.10000116).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAT3NM_138422.4 linkuse as main transcriptc.56C>T p.Pro19Leu missense_variant 2/2 ENST00000329478.4 NP_612431.2
SCAMP4NM_079834.4 linkuse as main transcriptc.-41-2876C>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.56C>T p.Pro19Leu missense_variant 2/21 NM_138422.4 ENSP00000332448 P1
SCAMP4ENST00000316097.13 linkuse as main transcriptc.-41-2876C>T intron_variant 1 NM_079834.4 ENSP00000316007 P1Q969E2-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152268
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000551
AC:
6
AN:
108980
Hom.:
0
AF XY:
0.0000497
AC XY:
3
AN XY:
60352
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000212
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000462
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000435
AC:
59
AN:
1356070
Hom.:
0
Cov.:
30
AF XY:
0.0000464
AC XY:
31
AN XY:
667820
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000981
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:
0.0000507
Gnomad4 OTH exome
AF:
0.0000354
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152268
Hom.:
0
Cov.:
34
AF XY:
0.0000134
AC XY:
1
AN XY:
74398
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000378
ExAC
AF:
0.0000182
AC:
2

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 GeneticsApr 12, 2023The c.8C>T (p.P3L) alteration is located in exon 2 (coding exon 1) of the ADAT3 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the proline (P) at amino acid position 3 to be replaced by a leucine (L). 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
-0.31
T
BayesDel_noAF
Benign
-0.39
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.20
.;T
Eigen
Benign
-0.43
Eigen_PC
Benign
-0.51
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.52
T;T
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.10
T;T
MetaSVM
Benign
-0.96
T
MutationTaster
Benign
0.94
D;D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
0.15
N;N
REVEL
Benign
0.10
Sift
Benign
0.37
T;T
Sift4G
Pathogenic
0.0
D;D
Vest4
0.31
MVP
0.36
MPC
0.41
ClinPred
0.066
T
GERP RS
0.36
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
gMVP
0.37

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs752745048; hg19: chr19-1912102; API