NM_003054.6:c.1441-2864T>C

Variant names:

• chr10-117274298-T-C
• rs363276
• NM_003054.6:c.1441-2864T>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.1441-2864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,078 control chromosomes in the GnomAD database, including 45,660 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 0.77 (45660 hom., cov: 31)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298
• Publications: 18 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.1441-2864T>C		intron_variant	Intron 15 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.1441-2864T>C		intron_variant	Intron 15 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1857-2864T>C		intron_variant	Intron 14 of 14	2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116921 AN: 151962 Hom.: 45634 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.764

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

GnomAD4 genome AF: 0.769 AC: 116998 AN: 152078 Hom.: 45660 Cov.: 31 AF XY: 0.765 AC XY: 56874 AN XY: 74318

African (AFR) AF: 0.650 AC: 26941 AN: 41436

American (AMR) AF: 0.742 AC: 11343 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.827 AC: 2870 AN: 3470

East Asian (EAS) AF: 0.566 AC: 2920 AN: 5162

South Asian (SAS) AF: 0.740 AC: 3567 AN: 4818

European-Finnish (FIN) AF: 0.842 AC: 8913 AN: 10590

Middle Eastern (MID) AF: 0.774 AC: 226 AN: 292

European-Non Finnish (NFE) AF: 0.850 AC: 57773 AN: 67996

Other (OTH) AF: 0.763 AC: 1611 AN: 2112

Alfa AF: 0.823 Hom.: 24815

Bravo AF: 0.758

Asia WGS AF: 0.636 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.50
PhyloP100		-0.30
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: rs363276; hg19: chr10-119033809;