Variant 10-117241640-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.241

Variant links:

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 links:

SLC18A2-AS1 (HGNC:55843): (SLC18A2 antisense RNA 1)

SLC18A2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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	Effect	MANE	Protein
SLC18A2	NM_003054.6 linkuse as main transcript	c.-15-39A>C	intron_variant	ENST00000644641.2	NP_003045.2
SLC18A2-AS1	NR_184309.1 linkuse as main transcript	n.113+245T>G	intron_variant, non_coding_transcript_variant
SLC18A2-AS1	NR_184310.1 linkuse as main transcript	n.236+21T>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2 linkuse as main transcript	c.-15-39A>C	intron_variant		NM_003054.6	ENSP00000496339	P1	Q05940-1
SLC18A2-AS1	ENST00000425264.2 linkuse as main transcript	n.237+21T>G	intron_variant, non_coding_transcript_variant	3
SLC18A2	ENST00000497497.1 linkuse as main transcript	n.129-39A>C	intron_variant, non_coding_transcript_variant	2
SLC18A2-AS1	ENST00000691914.2 linkuse as main transcript	n.113+245T>G	intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.953

AC:

144885

AN:

151958

Hom.:

69439

Cov.:

show subpopulations

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.:

AF XY:

0.996

AC XY:

663890

AN XY:

666624

show subpopulations

Gnomad4 AFR exome

AF:

0.819

Gnomad4 AMR exome

AF:

0.991

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

0.989

GnomAD4 genome

AF:

0.953

AC:

144984

AN:

152066

Hom.:

69485

Cov.:

AF XY:

0.956

AC XY:

71072

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.837

Gnomad4 AMR

AF:

0.987

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.999

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

0.999

Gnomad4 OTH

AF:

0.964

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

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Brain dopamine-serotonin vesicular transport disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

8.6

DANN

Benign

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over