rs17092144

Variant names:

• chr8-20180933-C-A
• NM_003053.4:c.32G>T

Your query was ambiguous. Multiple possible variants found:

• chr8-20180933-C-A
• chr8-20180933-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003053.4(SLC18A1):​c.32G>T​(p.Arg11Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R11Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLC18A1 NM_003053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

Genes affected

SLC18A1 (HGNC:10934): (solute carrier family 18 member A1) The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08804518).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.32G>T	p.Arg11Leu	missense_variant	Exon 2 of 16	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.32G>T	p.Arg11Leu	missense_variant	Exon 2 of 16	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446274 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 718098

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000239

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	2.9
DANN	Benign	0.96
DEOGEN2	Benign	0.11	.;T;T;.;.;.;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.053	N
LIST_S2	Benign	0.69	.;.;T;T;T;.;T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.088	T;T;T;T;T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;.
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.7	N;N;N;N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.048	D;T;T;D;D;D;D
Sift4G	Benign	0.090	T;T;T;T;T;T;T
Polyphen		0.018	.;B;B;.;.;.;.
Vest4		0.20
MutPred		0.32		Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);
MVP		0.16
MPC		0.0019
ClinPred		0.19	T
GERP RS		-4.3
Varity_R		0.053
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-20038444;