NM_003054.6:c.991+4334C>T

Variant names:

• chr10-117262226-C-T
• rs2015586
• NM_003054.6:c.991+4334C>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+4334C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 149,248 control chromosomes in the GnomAD database, including 24,385 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 0.58 (24385 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.137
• Publications: 11 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.594 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.991+4334C>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+4334C>T		intron_variant	Intron 10 of 15		NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1407+4334C>T		intron_variant	Intron 9 of 14	2

Frequencies

GnomAD3 genomes AF: 0.575 AC: 85779 AN: 149134 Hom.: 24367 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.772

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.620

Gnomad MID AF: 0.429

Gnomad NFE AF: 0.599

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.575 AC: 85840 AN: 149248 Hom.: 24385 Cov.: 33 AF XY: 0.576 AC XY: 41951 AN XY: 72846

African (AFR) AF: 0.536 AC: 21857 AN: 40778

American (AMR) AF: 0.585 AC: 8789 AN: 15018

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1662 AN: 3412

East Asian (EAS) AF: 0.515 AC: 2657 AN: 5164

South Asian (SAS) AF: 0.560 AC: 2659 AN: 4750

European-Finnish (FIN) AF: 0.620 AC: 6282 AN: 10136

Middle Eastern (MID) AF: 0.420 AC: 120 AN: 286

European-Non Finnish (NFE) AF: 0.599 AC: 39936 AN: 66724

Other (OTH) AF: 0.568 AC: 1177 AN: 2072

Alfa AF: 0.576 Hom.: 41644

Bravo AF: 0.564

Asia WGS AF: 0.524 AC: 1822 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-0.14
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: rs2015586; hg19: chr10-119021737;