NM_138422.4:c.111T>G

Variant names:

• chr19-1912158-T-G
• rs760510020
• NM_138422.4:c.111T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_138422.4(ADAT3):​c.111T>G​(p.Pro37Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00028 in 1,569,764 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: 𝑓 0.00020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00029 (0 hom.)
• Consequence: ADAT3 NM_138422.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.85
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 19-1912158-T-G is Benign according to our data. Variant chr19-1912158-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 726301.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.85 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.111T>G	p.Pro37Pro	synonymous	Exon 2 of 2	NP_612431.2	D6W601
	SCAMP4	NM_079834.4	MANE Select	c.-41-2821T>G		intron	N/A	NP_524558.1	Q969E2-1
	ADAT3	NM_001329533.2		c.63T>G	p.Pro21Pro	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.111T>G	p.Pro37Pro	synonymous	Exon 2 of 2	ENSP00000332448.2	D6W601
	SCAMP4	ENST00000316097.13	TSL:1 MANE Select	c.-41-2821T>G		intron	N/A	ENSP00000316007.7	Q969E2-1
	SCAMP4	ENST00000414057.6	TSL:1	c.-125-5536T>G		intron	N/A	ENSP00000479672.1	A0A087WVT5

Frequencies

GnomAD3 genomes AF: 0.000204 AC: 31 AN: 152264 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000559 AC: 96 AN: 171790 AF XY: 0.000604

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000221

Gnomad ASJ exome AF: 0.00541

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000151

Gnomad OTH exome AF: 0.000431

GnomAD4 exome AF: 0.000289 AC: 409 AN: 1417500 Hom.: 0 Cov.: 30 AF XY: 0.000310 AC XY: 218 AN XY: 702250

African (AFR) AF: 0.00 AC: 0 AN: 32440

American (AMR) AF: 0.000311 AC: 12 AN: 38582

Ashkenazi Jewish (ASJ) AF: 0.00498 AC: 126 AN: 25286

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37898

South Asian (SAS) AF: 0.00121 AC: 98 AN: 80980

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42896

Middle Eastern (MID) AF: 0.000876 AC: 5 AN: 5706

European-Non Finnish (NFE) AF: 0.000112 AC: 123 AN: 1094764

Other (OTH) AF: 0.000746 AC: 44 AN: 58948

GnomAD4 genome AF: 0.000204 AC: 31 AN: 152264 Hom.: 0 Cov.: 33 AF XY: 0.000188 AC XY: 14 AN XY: 74402

African (AFR) AF: 0.0000241 AC: 1 AN: 41472

American (AMR) AF: 0.000131 AC: 2 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68044

Other (OTH) AF: 0.000478 AC: 1 AN: 2092

Alfa AF: 0.000824 Hom.: 0

Bravo AF: 0.000238

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.39
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism

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: rs760510020; hg19: chr19-1912157;