NM_003054.6:c.991+628C>T

Variant names:

• chr10-117258520-C-T
• rs363221
• NM_003054.6:c.991+628C>T

Variant summary

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

The NM_003054.6(SLC18A2):​c.991+628C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0494 in 152,240 control chromosomes in the GnomAD database, including 274 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 0.049 (274 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• Publications: 4 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.991+628C>T		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.991+628C>T		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1407+628C>T		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes AF: 0.0495 AC: 7527 AN: 152120 Hom.: 275 Cov.: 33

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.158

Gnomad AMR AF: 0.0357

Gnomad ASJ AF: 0.0409

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0382

Gnomad FIN AF: 0.0518

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0625

Gnomad OTH AF: 0.0468

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

GnomAD4 genome AF: 0.0494 AC: 7521 AN: 152240 Hom.: 274 Cov.: 33 AF XY: 0.0491 AC XY: 3655 AN XY: 74412

African (AFR) AF: 0.0150 AC: 623 AN: 41560

American (AMR) AF: 0.0358 AC: 547 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0409 AC: 142 AN: 3472

East Asian (EAS) AF: 0.187 AC: 967 AN: 5172

South Asian (SAS) AF: 0.0378 AC: 182 AN: 4818

European-Finnish (FIN) AF: 0.0518 AC: 548 AN: 10586

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0625 AC: 4252 AN: 68016

Other (OTH) AF: 0.0487 AC: 103 AN: 2114

Alfa AF: 0.0583 Hom.: 644

Bravo AF: 0.0473

Asia WGS AF: 0.118 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.40
DANN	Benign	0.40
PhyloP100		-1.1
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: rs363221; hg19: chr10-119018031;