10-117263062-C-A

Variant names:

• chr10-117263062-C-A
• rs363224
• NM_003054.6:c.992-3671C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.992-3671C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 152,054 control chromosomes in the GnomAD database, including 18,709 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18709 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.79
• Publications: 12 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: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

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

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.992-3671C>A		intron_variant	Intron 10 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.992-3671C>A		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1408-3671C>A		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73748 AN: 151936 Hom.: 18699 Cov.: 33

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.748

Gnomad AMR AF: 0.528

Gnomad ASJ AF: 0.459

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.505

Gnomad FIN AF: 0.529

Gnomad MID AF: 0.375

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.485 AC: 73787 AN: 152054 Hom.: 18709 Cov.: 33 AF XY: 0.484 AC XY: 35991 AN XY: 74300

African (AFR) AF: 0.335 AC: 13898 AN: 41472

American (AMR) AF: 0.528 AC: 8077 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1592 AN: 3466

East Asian (EAS) AF: 0.452 AC: 2328 AN: 5156

South Asian (SAS) AF: 0.505 AC: 2432 AN: 4818

European-Finnish (FIN) AF: 0.529 AC: 5592 AN: 10570

Middle Eastern (MID) AF: 0.366 AC: 106 AN: 290

European-Non Finnish (NFE) AF: 0.560 AC: 38071 AN: 67972

Other (OTH) AF: 0.479 AC: 1010 AN: 2110

Alfa AF: 0.534 Hom.: 45040

Bravo AF: 0.483

Asia WGS AF: 0.461 AC: 1605 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.20
DANN	Benign	0.59
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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: rs363224; hg19: chr10-119022573;