rs200992550

Positions:

• chr19-1912430-G-A
• chr19-1912430-G-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000329478.4(ADAT3):​c.383G>A​(p.Arg128Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000515 in 1,359,006 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R128L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000052 (0 hom.)
• Consequence: ADAT3 ENST00000329478.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.191

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]

ACMG classification

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=0.05262792).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAT3	NM_138422.4	c.383G>A	p.Arg128Gln	missense_variant	2/2	ENST00000329478.4	NP_612431.2
SCAMP4	NM_079834.4	c.-41-2549G>A		intron_variant		ENST00000316097.13	NP_524558.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAT3	ENST00000329478.4	c.383G>A	p.Arg128Gln	missense_variant	2/2	1	NM_138422.4	ENSP00000332448	P1
SCAMP4	ENST00000316097.13	c.-41-2549G>A		intron_variant		1	NM_079834.4	ENSP00000316007	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000515 AC: 7 AN: 1359006 Hom.: 0 Cov.: 30 AF XY: 0.00000746 AC XY: 5 AN XY: 670410

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000300

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000307

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000468

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.37
DANN	Benign	0.81
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.38	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.70	T
REVEL	Benign	0.025
Sift4G	Benign	0.58	T
Vest4		0.13
MVP		0.19
MPC		0.45
ClinPred		0.066	T
GERP RS		-8.5
gMVP		0.22

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

Other links and lift over

dbSNP: rs200992550; hg19: chr19-1912429;