rs748742711

Variant names:

• chr19-1912212-C-T
• rs748742711
• NM_138422.4:c.165C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_138422.4(ADAT3):​c.165C>T​(p.Asp55Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000834 in 1,439,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000083 (0 hom.)
• Consequence: ADAT3 NM_138422.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.06
• 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: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 19-1912212-C-T is Benign according to our data. Variant chr19-1912212-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3389280.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.07 with no splicing effect.

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.165C>T	p.Asp55Asp	synonymous	Exon 2 of 2	NP_612431.2	D6W601
	SCAMP4	NM_079834.4	MANE Select	c.-41-2767C>T		intron	N/A	NP_524558.1	Q969E2-1
	ADAT3	NM_001329533.2		c.117C>T	p.Asp39Asp	synonymous	Exon 2 of 2	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.165C>T	p.Asp55Asp	synonymous	Exon 2 of 2	ENSP00000332448.2	D6W601
	SCAMP4	ENST00000316097.13	TSL:1 MANE Select	c.-41-2767C>T		intron	N/A	ENSP00000316007.7	Q969E2-1
	SCAMP4	ENST00000414057.6	TSL:1	c.-125-5482C>T		intron	N/A	ENSP00000479672.1	A0A087WVT5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000985 AC: 2 AN: 203040 AF XY: 0.00000895

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000687

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000194

GnomAD4 exome AF: 0.00000834 AC: 12 AN: 1439652 Hom.: 0 Cov.: 30 AF XY: 0.00000979 AC XY: 7 AN XY: 714824

African (AFR) AF: 0.00 AC: 0 AN: 33036

American (AMR) AF: 0.00 AC: 0 AN: 42108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25708

East Asian (EAS) AF: 0.00 AC: 0 AN: 38754

South Asian (SAS) AF: 0.00 AC: 0 AN: 83402

European-Finnish (FIN) AF: 0.0000641 AC: 3 AN: 46830

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00000724 AC: 8 AN: 1104478

Other (OTH) AF: 0.0000168 AC: 1 AN: 59588

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000508 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	4.3
DANN	Benign	0.89
PhyloP100		-1.1

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

Other links and lift over

dbSNP: rs748742711; hg19: chr19-1912211;