chr10-117261896-A-C

Variant names:

• chr10-117261896-A-C
• rs10082463
• NM_003054.6:c.991+4004A>C

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+4004A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,126 control chromosomes in the GnomAD database, including 1,541 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 0.13 (1541 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.80
• Publications: 5 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 = 0.382 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	NM_003054.6	MANE Select	c.991+4004A>C		intron	N/A	NP_003045.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.991+4004A>C		intron	N/A	ENSP00000496339.1
	SLC18A2	ENST00000497497.1	TSL:2	n.1407+4004A>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19353 AN: 152006 Hom.: 1538 Cov.: 33

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.0954

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.127 AC: 19376 AN: 152126 Hom.: 1541 Cov.: 33 AF XY: 0.131 AC XY: 9738 AN XY: 74356

African (AFR) AF: 0.138 AC: 5706 AN: 41472

American (AMR) AF: 0.190 AC: 2896 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3470

East Asian (EAS) AF: 0.397 AC: 2049 AN: 5164

South Asian (SAS) AF: 0.179 AC: 863 AN: 4824

European-Finnish (FIN) AF: 0.0527 AC: 559 AN: 10606

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.0954 AC: 6490 AN: 67998

Other (OTH) AF: 0.127 AC: 267 AN: 2108

Alfa AF: 0.105 Hom.: 1865

Bravo AF: 0.139

Asia WGS AF: 0.274 AC: 952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.16
DANN	Benign	0.45
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: rs10082463; hg19: chr10-119021407;