rs6586896

Variant names:

• chr8-20147130-T-A
• rs6586896
• NM_003053.4:c.1464+128A>T

Your query was ambiguous. Multiple possible variants found:

• chr8-20147130-T-A
• chr8-20147130-T-C
• chr8-20147130-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003053.4(SLC18A1):​c.1464+128A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 844,888 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: 32)
  • Exomes 𝑓: 0.0000012 (0 hom.)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.1464+128A>T		intron_variant	Intron 15 of 15	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.1464+128A>T		intron_variant	Intron 15 of 15	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000118 AC: 1 AN: 844888 Hom.: 0 AF XY: 0.00000237 AC XY: 1 AN XY: 421232

African (AFR) AF: 0.00 AC: 0 AN: 19982

American (AMR) AF: 0.00 AC: 0 AN: 15090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15314

East Asian (EAS) AF: 0.00 AC: 0 AN: 31682

South Asian (SAS) AF: 0.00 AC: 0 AN: 44700

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35142

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3128

European-Non Finnish (NFE) AF: 0.00000156 AC: 1 AN: 641498

Other (OTH) AF: 0.00 AC: 0 AN: 38352

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.26
DANN	Benign	0.30
PhyloP100		-0.57

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: rs6586896; hg19: chr8-20004641;