rs363343

Variant names:

• chr10-117255437-C-A
• rs363343
• NM_003054.6:c.791-42C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):​c.791-42C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 1,613,468 control chromosomes in the GnomAD database, including 506,248 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42426 hom., cov: 35)
  • Exomes 𝑓: 0.79 (463822 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0780
• Publications: 15 publications found

Genes affected

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

SLC18A2 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-117255437-C-A is Benign according to our data. Variant chr10-117255437-C-A is described in ClinVar as Benign. ClinVar VariationId is 1238275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.815 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003054.6. 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
	SLC18A2	NM_003054.6	MANE Select	c.791-42C>A		intron	N/A	NP_003045.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.791-42C>A		intron	N/A	ENSP00000496339.1	Q05940-1
	SLC18A2	ENST00000853677.1		c.887-42C>A		intron	N/A	ENSP00000523736.1
	SLC18A2	ENST00000853679.1		c.884-42C>A		intron	N/A	ENSP00000523738.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112450 AN: 151816 Hom.: 42438 Cov.: 35

Gnomad AFR AF: 0.645

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.713

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.803

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.821

Gnomad OTH AF: 0.764

GnomAD2 exomes AF: 0.738 AC: 184675 AN: 250348 AF XY: 0.744

Gnomad AFR exome AF: 0.648

Gnomad AMR exome AF: 0.655

Gnomad ASJ exome AF: 0.827

Gnomad EAS exome AF: 0.401

Gnomad FIN exome AF: 0.803

Gnomad NFE exome AF: 0.822

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.792 AC: 1157966 AN: 1461534 Hom.: 463822 Cov.: 47 AF XY: 0.791 AC XY: 574977 AN XY: 727052

African (AFR) AF: 0.646 AC: 21602 AN: 33460

American (AMR) AF: 0.661 AC: 29505 AN: 44656

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 21532 AN: 26134

East Asian (EAS) AF: 0.440 AC: 17446 AN: 39694

South Asian (SAS) AF: 0.686 AC: 59186 AN: 86242

European-Finnish (FIN) AF: 0.807 AC: 43094 AN: 53384

Middle Eastern (MID) AF: 0.821 AC: 4734 AN: 5766

European-Non Finnish (NFE) AF: 0.822 AC: 914307 AN: 1111808

Other (OTH) AF: 0.771 AC: 46560 AN: 60390

GnomAD4 genome AF: 0.740 AC: 112467 AN: 151934 Hom.: 42426 Cov.: 35 AF XY: 0.734 AC XY: 54522 AN XY: 74254

African (AFR) AF: 0.644 AC: 26692 AN: 41438

American (AMR) AF: 0.712 AC: 10875 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.826 AC: 2860 AN: 3464

East Asian (EAS) AF: 0.406 AC: 2096 AN: 5158

South Asian (SAS) AF: 0.659 AC: 3177 AN: 4822

European-Finnish (FIN) AF: 0.803 AC: 8480 AN: 10560

Middle Eastern (MID) AF: 0.871 AC: 256 AN: 294

European-Non Finnish (NFE) AF: 0.821 AC: 55746 AN: 67908

Other (OTH) AF: 0.761 AC: 1605 AN: 2110

Alfa AF: 0.793 Hom.: 193571

Bravo AF: 0.727

Asia WGS AF: 0.511 AC: 1782 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Brain dopamine-serotonin vesicular transport disease (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	16
DANN	Benign	0.62
PhyloP100		0.078
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs363343; hg19: chr10-119014948; COSMIC: COSV53688880;