NM_003054.6:c.33G>T

Variant names:

• chr10-117241726-G-T
• rs2133723906
• NM_003054.6:c.33G>T

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003054.6(SLC18A2):​c.33G>T​(p.Trp11Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000688 in 1,454,202 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC18A2 NM_003054.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.94
• Publications: 0 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-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.33G>T	p.Trp11Cys	missense_variant	Exon 2 of 16	ENST00000644641.2	NP_003045.2
SLC18A2-AS1	NR_184310.1	n.171C>A		non_coding_transcript_exon_variant	Exon 2 of 3
SLC18A2-AS1	NR_184309.1	n.113+159C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.33G>T	p.Trp11Cys	missense_variant	Exon 2 of 16		NM_003054.6	ENSP00000496339.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454202 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723020

African (AFR) AF: 0.00 AC: 0 AN: 33072

American (AMR) AF: 0.00 AC: 0 AN: 44208

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25890

East Asian (EAS) AF: 0.00 AC: 0 AN: 39240

South Asian (SAS) AF: 0.00 AC: 0 AN: 85400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5212

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109574

Other (OTH) AF: 0.00 AC: 0 AN: 60046

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	34
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.47	T;T
Eigen	Benign	-0.015
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L;L
PhyloP100		5.9
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-4.2	D;.
REVEL	Benign	0.17
Sift	Benign	0.069	T;.
Sift4G	Benign	0.13	T;.
Polyphen		0.0080	B;B
Vest4		0.46
MutPred		0.69		Gain of helix (P = 0.0225);Gain of helix (P = 0.0225);
MVP		0.043
MPC		0.59
ClinPred		0.95	D
GERP RS		4.3
Varity_R		0.30
gMVP		0.77
Mutation Taster		=38/62	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.52		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.52		Position offset: 7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2133723906; hg19: chr10-119001237;