rs3779672

Positions:

• chr8-20174592-T-C
• chr8-20174592-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003053.4(SLC18A1):​c.548-148A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 608,898 control chromosomes in the GnomAD database, including 7,683 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 0.14 (1709 hom., cov: 32)
  • Exomes 𝑓: 0.15 (5974 hom.)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.548-148A>G		intron_variant		ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.548-148A>G		intron_variant		1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21745 AN: 151984 Hom.: 1709 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.146

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.0876

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.151 AC: 68969 AN: 456796 Hom.: 5974 AF XY: 0.149 AC XY: 36072 AN XY: 241988

Gnomad4 AFR exome AF: 0.0982

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.224

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.0806

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.175

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.143 AC: 21750 AN: 152102 Hom.: 1709 Cov.: 32 AF XY: 0.138 AC XY: 10264 AN XY: 74368

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.145

Gnomad4 ASJ AF: 0.235

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.0872

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.173

Alfa AF: 0.173 Hom.: 4794

Bravo AF: 0.148

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.64

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

Publications

LitVar

Other links and lift over

dbSNP: rs3779672; hg19: chr8-20032103;