19-1912106-C-T

Position:

chr19-1912106-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138422.4(ADAT3):c.59C>T(p.Ala20Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,517,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

ADAT3
NM_138422.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0310

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]

ADAT3 links:

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]

SCAMP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03539309).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAT3	NM_138422.4 linkuse as main transcript	c.59C>T	p.Ala20Val	missense_variant	2/2	ENST00000329478.4	NP_612431.2
SCAMP4	NM_079834.4 linkuse as main transcript	c.-41-2873C>T		intron_variant		ENST00000316097.13	NP_524558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAT3	ENST00000329478.4 linkuse as main transcript	c.59C>T	p.Ala20Val	missense_variant	2/2	1	NM_138422.4	ENSP00000332448	P1
SCAMP4	ENST00000316097.13 linkuse as main transcript	c.-41-2873C>T		intron_variant		1	NM_079834.4	ENSP00000316007	P1	Q969E2-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152268

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000203

AC:

AN:

118070

Hom.:

AF XY:

0.000169

AC XY:

AN XY:

65224

show subpopulations

Gnomad AFR exome

AF:

0.000194

Gnomad AMR exome

AF:

0.00113

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000293

AC:

AN:

1365552

Hom.:

Cov.:

AF XY:

0.0000327

AC XY:

AN XY:

673046

show subpopulations

Gnomad4 AFR exome

AF:

0.0000334

Gnomad4 AMR exome

AF:

0.00115

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:

0.00000187

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000262

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.0000180

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Mar 17, 2016

- -

Intellectual disability-strabismus syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 05, 2018

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.1

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-0.94

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.0031

MetaRNN

Benign

0.035

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.46

REVEL

Benign

0.080

Sift4G

Benign

0.14

T;T

Vest4

0.10

MVP

0.17

MPC

0.41

ClinPred

0.017

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.6

gMVP

0.15

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over