rs363279

chr10-117277114-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003054.6(SLC18A2):c.1441-48T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,077,238 control chromosomes in the GnomAD database, including 8,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1143 hom., cov: 32)
  • Exomes 𝑓: 0.11 (7056 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 10-117277114-T-C is Benign according to our data. Variant chr10-117277114-T-C is described in ClinVar as [Benign]. Clinvar id is 1283694.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.1441-48T>C		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.1441-48T>C		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1857-48T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16088 AN: 152144 Hom.: 1140 Cov.: 32

Gnomad AFR AF: 0.0848

Gnomad AMI AF: 0.0330

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0879

Gnomad OTH AF: 0.113

GnomAD3 exomes AF: 0.130 AC: 26649 AN: 205080 Hom.: 2382 AF XY: 0.128 AC XY: 14216 AN XY: 111250

Gnomad AFR exome AF: 0.0847

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.124

Gnomad EAS exome AF: 0.352

Gnomad SAS exome AF: 0.158

Gnomad FIN exome AF: 0.0532

Gnomad NFE exome AF: 0.0888

Gnomad OTH exome AF: 0.127

GnomAD4 exome AF: 0.108 AC: 99844 AN: 924976 Hom.: 7056 Cov.: 12 AF XY: 0.109 AC XY: 52299 AN XY: 479904

Gnomad4 AFR exome AF: 0.0839

Gnomad4 AMR exome AF: 0.202

Gnomad4 ASJ exome AF: 0.121

Gnomad4 EAS exome AF: 0.342

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.0552

Gnomad4 NFE exome AF: 0.0883

Gnomad4 OTH exome AF: 0.120

GnomAD4 genome AF: 0.106 AC: 16101 AN: 152262 Hom.: 1143 Cov.: 32 AF XY: 0.110 AC XY: 8181 AN XY: 74454

Gnomad4 AFR AF: 0.0847

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.341

Gnomad4 SAS AF: 0.167

Gnomad4 FIN AF: 0.0503

Gnomad4 NFE AF: 0.0879

Gnomad4 OTH AF: 0.112

Alfa AF: 0.0961 Hom.: 207

Bravo AF: 0.115

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.6
Dann	Benign	0.81

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: rs363279; hg19: chr10-119036625; COSMIC: COSV53689272; COSMIC: COSV53689272;