Variant 19-1912166-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_138422.4(ADAT3):c.119C>T(p.Ala40Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000223 in 1,572,158 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

ADAT3
NM_138422.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.660

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059817433).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAT3	NM_138422.4 link	c.119C>T	p.Ala40Val	missense_variant	2/2	ENST00000329478.4	NP_612431.2	Q96EY9D6W601
SCAMP4	NM_079834.4 link	c.-41-2813C>T		intron_variant		ENST00000316097.13	NP_524558.1	Q969E2-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAT3	ENST00000329478.4 link	c.119C>T	p.Ala40Val	missense_variant	2/2	1	NM_138422.4	ENSP00000332448.2		D6W601
SCAMP4	ENST00000316097.13 link	c.-41-2813C>T		intron_variant		1	NM_079834.4	ENSP00000316007.7		Q969E2-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000250

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000351

AC:

AN:

173970

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

95538

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000730

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000732

Gnomad SAS exome

AF:

0.000568

Gnomad FIN exome

AF:

0.0000867

Gnomad NFE exome

AF:

0.000284

Gnomad OTH exome

AF:

0.000855

GnomAD4 exome

AF:

0.000226

AC:

321

AN:

1419774

Hom.:

Cov.:

AF XY:

0.000236

AC XY:

166

AN XY:

703600

show subpopulations

Gnomad4 AFR exome

AF:

0.0000308

Gnomad4 AMR exome

AF:

0.000591

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000211

Gnomad4 SAS exome

AF:

0.000431

Gnomad4 FIN exome

AF:

0.0000461

Gnomad4 NFE exome

AF:

0.000214

Gnomad4 OTH exome

AF:

0.000288

GnomAD4 genome

AF:

0.000197

AC:

AN:

152384

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000250

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000262

Hom.:

Bravo

AF:

0.000257

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000340

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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 submitter

clinical testing

Ambry Genetics

Jul 09, 2024

The c.71C>T (p.A24V) 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 71, causing the alanine (A) at amino acid position 24 to be replaced by a valine (V). 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

-0.51

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.77

DANN

Benign

0.84

DEOGEN2

Benign

0.011

.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.022

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0015

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-1.1

PrimateAI

Benign

0.44

REVEL

Benign

0.033

Sift4G

Benign

0.31

T;T

Vest4

0.063

MVP

0.24

MPC

0.39

ClinPred

0.0037

GERP RS

-7.1

gMVP

0.18

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.

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