10-117241720-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS1

The NM_003054.6(SLC18A2):c.27C>T(p.Val9=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000144 in 1,604,790 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00014 (4 hom.)
• Consequence: SLC18A2 NM_003054.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.225

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 10-117241720-C-T is Benign according to our data. Variant chr10-117241720-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 747914.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.225 with no splicing effect.
• BS1: Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00014 (204/1452478) while in subpopulation MID AF= 0.00859 (44/5124). AF 95% confidence interval is 0.00657. There are 4 homozygotes in gnomad4_exome. There are 117 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.27C>T	p.Val9=	synonymous_variant	2/16	ENST00000644641.2
SLC18A2-AS1	NR_184309.1	n.113+165G>A		intron_variant, non_coding_transcript_variant
SLC18A2-AS1	NR_184310.1	n.177G>A		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.27C>T	p.Val9=	synonymous_variant	2/16		NM_003054.6	P1
SLC18A2-AS1	ENST00000425264.2	n.178G>A		non_coding_transcript_exon_variant	2/3	3
SLC18A2	ENST00000497497.1	n.170C>T		non_coding_transcript_exon_variant	2/15	2
SLC18A2-AS1	ENST00000691914.2	n.113+165G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000181 AC: 41 AN: 226398 Hom.: 0 AF XY: 0.000202 AC XY: 25 AN XY: 123936

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000241

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000591

Gnomad SAS exome AF: 0.0000342

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000285

Gnomad OTH exome AF: 0.000541

GnomAD4 exome AF: 0.000140 AC: 204 AN: 1452478 Hom.: 4 Cov.: 33 AF XY: 0.000162 AC XY: 117 AN XY: 721984

Gnomad4 AFR exome AF: 0.000121

Gnomad4 AMR exome AF: 0.000182

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000983

Gnomad4 OTH exome AF: 0.000467

GnomAD4 genome AF: 0.000177 AC: 27 AN: 152312 Hom.: 0 Cov.: 33 AF XY: 0.000215 AC XY: 16 AN XY: 74470

Gnomad4 AFR AF: 0.0000481

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000491 Hom.: 0

Bravo AF: 0.000162

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 09, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	16
Dann	Benign	0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs368087382; hg19: chr10-119001231;