19-1912909-GAG-AAA

Variant names:

• chr19-1912909-GAG-AAA
• NM_138422.4:c.862_864delGAGinsAAA
• ADAT3 p.Glu288Lys

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_138422.4(ADAT3):​c.862_864delGAGinsAAA​(p.Glu288Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: ADAT3 NM_138422.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.925
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138422.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAT3	NM_138422.4	MANE Select	c.862_864delGAGinsAAA	p.Glu288Lys	missense	N/A	NP_612431.2	D6W601
	SCAMP4	NM_079834.4	MANE Select	c.-41-2070_-41-2068delGAGinsAAA		intron	N/A	NP_524558.1	Q969E2-1
	ADAT3	NM_001329533.2		c.814_816delGAGinsAAA	p.Glu272Lys	missense	N/A	NP_001316462.1	Q96EY9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAT3	ENST00000329478.4	TSL:1 MANE Select	c.862_864delGAGinsAAA	p.Glu288Lys	missense	N/A	ENSP00000332448.2	D6W601
	SCAMP4	ENST00000316097.13	TSL:1 MANE Select	c.-41-2070_-41-2068delGAGinsAAA		intron	N/A	ENSP00000316007.7	Q969E2-1
	SCAMP4	ENST00000414057.6	TSL:1	c.-125-4785_-125-4783delGAGinsAAA		intron	N/A	ENSP00000479672.1	A0A087WVT5

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.93

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-1912908;