Variant 19-1912164-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_138422.4(ADAT3):c.117G>A(p.Pro39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 1,572,282 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0034 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0054 ( 21 hom. )

Consequence

ADAT3
NM_138422.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.94

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-1912164-G-A is Benign according to our data. Variant chr19-1912164-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 718244.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.94 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAT3	NM_138422.4 linkuse as main transcript	c.117G>A	p.Pro39=	synonymous_variant	2/2	ENST00000329478.4	NP_612431.2
SCAMP4	NM_079834.4 linkuse as main transcript	c.-41-2815G>A		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.117G>A	p.Pro39=	synonymous_variant	2/2	1	NM_138422.4	ENSP00000332448	P1
SCAMP4	ENST00000316097.13 linkuse as main transcript	c.-41-2815G>A		intron_variant		1	NM_079834.4	ENSP00000316007	P1	Q969E2-1

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

516

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000916

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00150

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00595

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00303

AC:

527

AN:

173958

Hom.:

AF XY:

0.00297

AC XY:

284

AN XY:

95574

show subpopulations

Gnomad AFR exome

AF:

0.000735

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00117

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.000730

Gnomad FIN exome

AF:

0.00166

Gnomad NFE exome

AF:

0.00585

Gnomad OTH exome

AF:

0.00128

GnomAD4 exome

AF:

0.00541

AC:

7686

AN:

1419900

Hom.:

Cov.:

AF XY:

0.00528

AC XY:

3718

AN XY:

703632

show subpopulations

Gnomad4 AFR exome

AF:

0.00108

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.00189

Gnomad4 EAS exome

AF:

0.0000527

Gnomad4 SAS exome

AF:

0.000801

Gnomad4 FIN exome

AF:

0.00169

Gnomad4 NFE exome

AF:

0.00651

Gnomad4 OTH exome

AF:

0.00468

GnomAD4 genome

AF:

0.00339

AC:

516

AN:

152382

Hom.:

Cov.:

AF XY:

0.00313

AC XY:

233

AN XY:

74520

show subpopulations

Gnomad4 AFR

AF:

0.000914

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00150

Gnomad4 NFE

AF:

0.00595

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00399

Hom.:

Bravo

AF:

0.00329

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2024	ADAT3: BP4, BP7, BS2; SCAMP4: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.11

DANN

Benign

0.74

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