NM_003054.6:c.464+271C>T

Variant names:

• chr10-117244584-C-T
• rs363333
• NM_003054.6:c.464+271C>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.464+271C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,226 control chromosomes in the GnomAD database, including 47,929 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 0.76 (47929 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.438
• Publications: 9 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.464+271C>T		intron_variant	Intron 3 of 15	ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.464+271C>T		intron_variant	Intron 3 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.607+271C>T		intron_variant	Intron 3 of 14	2

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115318 AN: 152108 Hom.: 47921 Cov.: 33

Gnomad AFR AF: 0.392

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 0.720

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.932

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.758 AC: 115341 AN: 152226 Hom.: 47929 Cov.: 33 AF XY: 0.760 AC XY: 56587 AN XY: 74426

African (AFR) AF: 0.391 AC: 16229 AN: 41498

American (AMR) AF: 0.772 AC: 11805 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3176 AN: 3472

East Asian (EAS) AF: 0.720 AC: 3722 AN: 5170

South Asian (SAS) AF: 0.902 AC: 4359 AN: 4832

European-Finnish (FIN) AF: 0.927 AC: 9846 AN: 10618

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.932 AC: 63422 AN: 68024

Other (OTH) AF: 0.778 AC: 1646 AN: 2116

Alfa AF: 0.875 Hom.: 99954

Bravo AF: 0.724

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.1
DANN	Benign	0.55
PhyloP100		0.44
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: rs363333; hg19: chr10-119004095;