rs1390938

Variant names:

• chr8-20179202-A-G
• rs1390938
• NM_003053.4:c.407T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003053.4(SLC18A1):​c.407T>C​(p.Ile136Thr) variant causes a missense change. The variant allele was found at a frequency of 0.746 in 1,613,946 control chromosomes in the GnomAD database, including 452,579 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.77 (46328 hom., cov: 31)
  • Exomes 𝑓: 0.74 (406251 hom.)
• Consequence: SLC18A1 NM_003053.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.64
• Publications: 70 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=9.979525E-7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.407T>C	p.Ile136Thr	missense_variant	Exon 3 of 16	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.407T>C	p.Ile136Thr	missense_variant	Exon 3 of 16	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes AF: 0.774 AC: 117626 AN: 151974 Hom.: 46276 Cov.: 31

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.768

GnomAD2 exomes AF: 0.714 AC: 179530 AN: 251432 AF XY: 0.715

Gnomad AFR exome AF: 0.912

Gnomad AMR exome AF: 0.497

Gnomad ASJ exome AF: 0.810

Gnomad EAS exome AF: 0.722

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.753

Gnomad OTH exome AF: 0.728

GnomAD4 exome AF: 0.743 AC: 1086328 AN: 1461854 Hom.: 406251 Cov.: 65 AF XY: 0.741 AC XY: 538907 AN XY: 727232

African (AFR) AF: 0.922 AC: 30854 AN: 33480

American (AMR) AF: 0.509 AC: 22750 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.810 AC: 21158 AN: 26136

East Asian (EAS) AF: 0.732 AC: 29070 AN: 39700

South Asian (SAS) AF: 0.678 AC: 58478 AN: 86258

European-Finnish (FIN) AF: 0.705 AC: 37642 AN: 53420

Middle Eastern (MID) AF: 0.785 AC: 4527 AN: 5768

European-Non Finnish (NFE) AF: 0.752 AC: 836523 AN: 1111980

Other (OTH) AF: 0.751 AC: 45326 AN: 60392

GnomAD4 genome AF: 0.774 AC: 117731 AN: 152092 Hom.: 46328 Cov.: 31 AF XY: 0.766 AC XY: 56919 AN XY: 74332

African (AFR) AF: 0.911 AC: 37839 AN: 41520

American (AMR) AF: 0.610 AC: 9322 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2791 AN: 3470

East Asian (EAS) AF: 0.718 AC: 3688 AN: 5136

South Asian (SAS) AF: 0.677 AC: 3265 AN: 4824

European-Finnish (FIN) AF: 0.706 AC: 7453 AN: 10554

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50819 AN: 67990

Other (OTH) AF: 0.770 AC: 1621 AN: 2106

Alfa AF: 0.759 Hom.: 221015

Bravo AF: 0.775

TwinsUK AF: 0.753 AC: 2793

ALSPAC AF: 0.750 AC: 2892

ESP6500AA AF: 0.908 AC: 4002

ESP6500EA AF: 0.761 AC: 6547

ExAC AF: 0.727 AC: 88213

Asia WGS AF: 0.719 AC: 2504 AN: 3478

EpiCase AF: 0.762

EpiControl AF: 0.772

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.11	.;T;T;.;.;.;.
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.36
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.15	.;.;T;T;T;.;T
MetaRNN	Benign	0.0000010	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-1.1	N;N;N;N;N;N;.
PhyloP100		5.6
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	3.0	N;N;N;N;N;N;N
REVEL	Benign	0.11
Sift	Benign	0.34	T;T;T;T;T;T;T
Sift4G	Benign	0.34	T;T;T;T;T;T;T
Polyphen		0.0	.;B;B;.;.;.;.
Vest4		0.18
MPC		0.0018
ClinPred		0.015	T
GERP RS		6.0
Varity_R		0.088
gMVP		0.72
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: rs1390938; hg19: chr8-20036713; COSMIC: COSV107224612; COSMIC: COSV107224612;