10-117255420-C-T

Position:

• chr10-117255420-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003054.6(SLC18A2):​c.790+54C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 1,613,372 control chromosomes in the GnomAD database, including 502,367 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42083 hom., cov: 35)
  • Exomes 𝑓: 0.79 (460284 hom.)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.807

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 10-117255420-C-T is Benign according to our data. Variant chr10-117255420-C-T is described in ClinVar as [Benign]. Clinvar id is 1237867.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.790+54C>T		intron_variant		ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.790+54C>T		intron_variant			NM_003054.6	ENSP00000496339	P1
SLC18A2	ENST00000497497.1	n.1206+54C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.738 AC: 111957 AN: 151802 Hom.: 42095 Cov.: 35

Gnomad AFR AF: 0.642

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.826

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.818

Gnomad OTH AF: 0.761

GnomAD4 exome AF: 0.789 AC: 1153526 AN: 1461452 Hom.: 460284 Cov.: 42 AF XY: 0.788 AC XY: 572786 AN XY: 727042

Gnomad4 AFR exome AF: 0.642

Gnomad4 AMR exome AF: 0.660

Gnomad4 ASJ exome AF: 0.824

Gnomad4 EAS exome AF: 0.439

Gnomad4 SAS exome AF: 0.684

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.819

Gnomad4 OTH exome AF: 0.768

GnomAD4 genome AF: 0.737 AC: 111972 AN: 151920 Hom.: 42083 Cov.: 35 AF XY: 0.731 AC XY: 54257 AN XY: 74240

Gnomad4 AFR AF: 0.641

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.826

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.818

Gnomad4 OTH AF: 0.756

Alfa AF: 0.774 Hom.: 5744

Bravo AF: 0.724

Asia WGS AF: 0.508 AC: 1772 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.56

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: rs363420; hg19: chr10-119014931; COSMIC: COSV53688871;