NM_003054.6:c.-15-39A>C

Variant names:

• chr10-117241640-A-C
• rs2619094
• NM_003054.6:c.-15-39A>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):​c.-15-39A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.991 in 1,504,598 control chromosomes in the GnomAD database, including 739,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (69485 hom., cov: 33)
  • Exomes 𝑓: 1.0 (670327 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.241
• Publications: 6 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-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-117241640-A-C is Benign according to our data. Variant chr10-117241640-A-C is described in ClinVar as [Benign]. Clinvar id is 1227431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.-15-39A>C		intron_variant	Intron 1 of 15	ENST00000644641.2	NP_003045.2
SLC18A2-AS1	NR_184309.1	n.113+245T>G		intron_variant	Intron 1 of 1
SLC18A2-AS1	NR_184310.1	n.236+21T>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.-15-39A>C		intron_variant	Intron 1 of 15		NM_003054.6	ENSP00000496339.1

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144885 AN: 151958 Hom.: 69439 Cov.: 33

Gnomad AFR AF: 0.837

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.987

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.978

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.964

GnomAD4 exome AF: 0.995 AC: 1346087 AN: 1352532 Hom.: 670327 Cov.: 39 AF XY: 0.996 AC XY: 663890 AN XY: 666624

African (AFR) AF: 0.819 AC: 22698 AN: 27722

American (AMR) AF: 0.991 AC: 31182 AN: 31474

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 23436 AN: 23436

East Asian (EAS) AF: 1.00 AC: 31100 AN: 31100

South Asian (SAS) AF: 1.00 AC: 75369 AN: 75400

European-Finnish (FIN) AF: 1.00 AC: 40009 AN: 40010

Middle Eastern (MID) AF: 0.991 AC: 3926 AN: 3962

European-Non Finnish (NFE) AF: 1.00 AC: 1062924 AN: 1063364

Other (OTH) AF: 0.989 AC: 55443 AN: 56064

GnomAD4 genome AF: 0.953 AC: 144984 AN: 152066 Hom.: 69485 Cov.: 33 AF XY: 0.956 AC XY: 71072 AN XY: 74348

African (AFR) AF: 0.837 AC: 34743 AN: 41488

American (AMR) AF: 0.987 AC: 15103 AN: 15302

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3472 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5086 AN: 5086

South Asian (SAS) AF: 0.999 AC: 4824 AN: 4828

European-Finnish (FIN) AF: 1.00 AC: 10616 AN: 10616

Middle Eastern (MID) AF: 0.976 AC: 283 AN: 290

European-Non Finnish (NFE) AF: 0.999 AC: 67909 AN: 67960

Other (OTH) AF: 0.964 AC: 2036 AN: 2112

Alfa AF: 0.942 Hom.: 4925

Bravo AF: 0.948

Asia WGS AF: 0.990 AC: 3429 AN: 3462

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 14, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Brain dopamine-serotonin vesicular transport disease Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	8.6
DANN	Benign	0.30
PhyloP100		-0.24
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: rs2619094; hg19: chr10-119001151;