chr10-117274298-T-C

Position:

• chr10-117274298-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.1441-2864T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,078 control chromosomes in the GnomAD database, including 45,660 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.77 (45660 hom., cov: 31)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.298

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.844 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A2	NM_003054.6	c.1441-2864T>C		intron_variant		ENST00000644641.2	NP_003045.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A2	ENST00000644641.2	c.1441-2864T>C		intron_variant			NM_003054.6	ENSP00000496339.1
SLC18A2	ENST00000497497.1	n.1857-2864T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116921 AN: 151962 Hom.: 45634 Cov.: 31

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.914

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.827

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.741

Gnomad FIN AF: 0.842

Gnomad MID AF: 0.768

Gnomad NFE AF: 0.850

Gnomad OTH AF: 0.764

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 116998 AN: 152078 Hom.: 45660 Cov.: 31 AF XY: 0.765 AC XY: 56874 AN XY: 74318

Gnomad4 AFR AF: 0.650

Gnomad4 AMR AF: 0.742

Gnomad4 ASJ AF: 0.827

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.740

Gnomad4 FIN AF: 0.842

Gnomad4 NFE AF: 0.850

Gnomad4 OTH AF: 0.763

Alfa AF: 0.823 Hom.: 21936

Bravo AF: 0.758

Asia WGS AF: 0.636 AC: 2215 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.50

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: rs363276; hg19: chr10-119033809;