10-117244053-T-G

Variant names:

• chr10-117244053-T-G
• rs363387
• NM_003054.6:c.204T>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003054.6(SLC18A2):​c.204T>G​(p.Thr68Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 1,614,058 control chromosomes in the GnomAD database, including 3,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (501 hom., cov: 33)
  • Exomes 𝑓: 0.050 (2943 hom.)
• Consequence: SLC18A2 NM_003054.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.21
• Publications: 15 publications found

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]

SLC18A2 Gene-Disease associations (from GenCC):

• brain dopamine-serotonin vesicular transport disease

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, G2P
• parkinsonism-dystonia, infantile, 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 10-117244053-T-G is Benign according to our data. Variant chr10-117244053-T-G is described in ClinVar as Benign. ClinVar VariationId is 1170119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.21 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.152 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003054.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	NM_003054.6	MANE Select	c.204T>G	p.Thr68Thr	synonymous	Exon 3 of 16	NP_003045.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A2	ENST00000644641.2	MANE Select	c.204T>G	p.Thr68Thr	synonymous	Exon 3 of 16	ENSP00000496339.1
	SLC18A2	ENST00000497497.1	TSL:2	n.347T>G		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes AF: 0.0664 AC: 10097 AN: 152108 Hom.: 496 Cov.: 33

Gnomad AFR AF: 0.0796

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.0593

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0284

Gnomad FIN AF: 0.0337

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0414

Gnomad OTH AF: 0.0837

GnomAD2 exomes AF: 0.0789 AC: 19828 AN: 251408 AF XY: 0.0701

Gnomad AFR exome AF: 0.0765

Gnomad AMR exome AF: 0.249

Gnomad ASJ exome AF: 0.0666

Gnomad EAS exome AF: 0.131

Gnomad FIN exome AF: 0.0352

Gnomad NFE exome AF: 0.0422

Gnomad OTH exome AF: 0.0740

GnomAD4 exome AF: 0.0500 AC: 73119 AN: 1461832 Hom.: 2943 Cov.: 32 AF XY: 0.0486 AC XY: 35309 AN XY: 727216

African (AFR) AF: 0.0791 AC: 2649 AN: 33480

American (AMR) AF: 0.234 AC: 10455 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 1699 AN: 26136

East Asian (EAS) AF: 0.106 AC: 4219 AN: 39698

South Asian (SAS) AF: 0.0292 AC: 2520 AN: 86254

European-Finnish (FIN) AF: 0.0353 AC: 1886 AN: 53408

Middle Eastern (MID) AF: 0.103 AC: 594 AN: 5768

European-Non Finnish (NFE) AF: 0.0409 AC: 45468 AN: 1111980

Other (OTH) AF: 0.0601 AC: 3629 AN: 60394

GnomAD4 genome AF: 0.0665 AC: 10126 AN: 152226 Hom.: 501 Cov.: 33 AF XY: 0.0688 AC XY: 5119 AN XY: 74446

African (AFR) AF: 0.0799 AC: 3319 AN: 41530

American (AMR) AF: 0.157 AC: 2402 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0593 AC: 206 AN: 3472

East Asian (EAS) AF: 0.127 AC: 657 AN: 5178

South Asian (SAS) AF: 0.0286 AC: 138 AN: 4826

European-Finnish (FIN) AF: 0.0337 AC: 358 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0414 AC: 2813 AN: 68006

Other (OTH) AF: 0.0851 AC: 180 AN: 2114

Alfa AF: 0.0528 Hom.: 329

Bravo AF: 0.0807

Asia WGS AF: 0.0910 AC: 314 AN: 3478

EpiCase AF: 0.0497

EpiControl AF: 0.0523

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

May 05, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.031
DANN	Benign	0.27
PhyloP100		-2.2
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: rs363387; hg19: chr10-119003564; COSMIC: COSV53690922; COSMIC: COSV53690922;