chr19-1912164-G-A

Variant names:

• chr19-1912164-G-A
• rs199915192
• NM_138422.4:c.117G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_138422.4(ADAT3):​c.117G>A​(p.Pro39Pro) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.94
• 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 -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 Benign/Likely_benign. ClinVar VariationId 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

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.117G>A	p.Pro39Pro	synonymous	Exon 2 of 2	NP_612431.2	D6W601
	SCAMP4	NM_079834.4	MANE Select	c.-41-2815G>A		intron	N/A	NP_524558.1	Q969E2-1
	ADAT3	NM_001329533.2		c.69G>A	p.Pro23Pro	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.117G>A	p.Pro39Pro	synonymous	Exon 2 of 2	ENSP00000332448.2	D6W601
	SCAMP4	ENST00000316097.13	TSL:1 MANE Select	c.-41-2815G>A		intron	N/A	ENSP00000316007.7	Q969E2-1
	SCAMP4	ENST00000414057.6	TSL:1	c.-125-5530G>A		intron	N/A	ENSP00000479672.1	A0A087WVT5

Frequencies

GnomAD3 genomes AF: 0.00339 AC: 516 AN: 152264 Hom.: 2 Cov.: 33

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

GnomAD2 exomes AF: 0.00303 AC: 527 AN: 173958 AF XY: 0.00297

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 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.: 21 Cov.: 30 AF XY: 0.00528 AC XY: 3718 AN XY: 703632

African (AFR) AF: 0.00108 AC: 35 AN: 32458

American (AMR) AF: 0.00121 AC: 47 AN: 38906

Ashkenazi Jewish (ASJ) AF: 0.00189 AC: 48 AN: 25352

East Asian (EAS) AF: 0.0000527 AC: 2 AN: 37964

South Asian (SAS) AF: 0.000801 AC: 65 AN: 81192

European-Finnish (FIN) AF: 0.00169 AC: 73 AN: 43240

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5712

European-Non Finnish (NFE) AF: 0.00651 AC: 7139 AN: 1096052

Other (OTH) AF: 0.00468 AC: 276 AN: 59024

GnomAD4 genome AF: 0.00339 AC: 516 AN: 152382 Hom.: 2 Cov.: 33 AF XY: 0.00313 AC XY: 233 AN XY: 74520

African (AFR) AF: 0.000914 AC: 38 AN: 41596

American (AMR) AF: 0.00216 AC: 33 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4830

European-Finnish (FIN) AF: 0.00150 AC: 16 AN: 10632

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00595 AC: 405 AN: 68034

Other (OTH) AF: 0.00237 AC: 5 AN: 2112

Alfa AF: 0.00399 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.74
PhyloP100		-4.9
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: rs199915192; hg19: chr19-1912163;