19-1912228-G-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_138422.4(ADAT3):​c.181G>T​(p.Ala61Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000582 in 1,595,378 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 34)
Exomes 𝑓: 0.00060 ( 1 hom. )

Consequence

ADAT3
NM_138422.4 missense

Scores

3
5
7

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 1.55
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 Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053672552).
BP6
Variant 19-1912228-G-T is Benign according to our data. Variant chr19-1912228-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2346490.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAT3NM_138422.4 linkuse as main transcriptc.181G>T p.Ala61Ser missense_variant 2/2 ENST00000329478.4 NP_612431.2
SCAMP4NM_079834.4 linkuse as main transcriptc.-41-2751G>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.181G>T p.Ala61Ser missense_variant 2/21 NM_138422.4 ENSP00000332448 P1
SCAMP4ENST00000316097.13 linkuse as main transcriptc.-41-2751G>T intron_variant 1 NM_079834.4 ENSP00000316007 P1Q969E2-1

Frequencies

GnomAD3 genomes
AF:
0.000427
AC:
65
AN:
152252
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00216
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000529
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000385
AC:
80
AN:
207704
Hom.:
0
AF XY:
0.000358
AC XY:
41
AN XY:
114478
show subpopulations
Gnomad AFR exome
AF:
0.0000824
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00164
Gnomad NFE exome
AF:
0.000585
Gnomad OTH exome
AF:
0.000191
GnomAD4 exome
AF:
0.000599
AC:
864
AN:
1443126
Hom.:
1
Cov.:
30
AF XY:
0.000621
AC XY:
445
AN XY:
716926
show subpopulations
Gnomad4 AFR exome
AF:
0.000151
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:
0.00163
Gnomad4 NFE exome
AF:
0.000686
Gnomad4 OTH exome
AF:
0.000385
GnomAD4 genome
AF:
0.000427
AC:
65
AN:
152252
Hom.:
0
Cov.:
34
AF XY:
0.000471
AC XY:
35
AN XY:
74384
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00216
Gnomad4 NFE
AF:
0.000529
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000665
Hom.:
0
Bravo
AF:
0.000249
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000702
AC:
6
ExAC
AF:
0.000410
AC:
49

ClinVar

Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, conflicting classifications
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJan 01, 2024- -
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsJul 04, 2022This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Uncertain
0.0
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.15
.;T
Eigen
Pathogenic
0.84
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.018
T
MetaRNN
Benign
0.054
T;T
MetaSVM
Uncertain
-0.12
T
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.58
T
REVEL
Benign
0.26
Sift4G
Uncertain
0.040
D;D
Vest4
0.52
MVP
0.64
MPC
1.0
ClinPred
0.15
T
GERP RS
5.0
gMVP
0.58

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

LitVar

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

Other links and lift over

dbSNP: rs149646876; hg19: chr19-1912227; API