rs15534

Positions:

• chr16-55702615-C-T

Variant summary

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

The ENST00000568943.6(SLC6A2):​c.*269C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 1,389,152 control chromosomes in the GnomAD database, including 21,543 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 0.21 (3749 hom., cov: 32)
  • Exomes 𝑓: 0.16 (17794 hom.)
• Consequence: SLC6A2 ENST00000568943.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597

Genes affected

SLC6A2 (HGNC:11048): (solute carrier family 6 member 2) This gene encodes a member of the sodium:neurotransmitter symporter family. This member is a multi-pass membrane protein, which is responsible for reuptake of norepinephrine into presynaptic nerve terminals and is a regulator of norepinephrine homeostasis. Mutations in this gene cause orthostatic intolerance, a syndrome characterized by lightheadedness, fatigue, altered mentation and syncope. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.33 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.*269C>T		3_prime_UTR_variant	15/15	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.*269C>T		3_prime_UTR_variant	15/15	1	NM_001172501.3	ENSP00000457473	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31223 AN: 151832 Hom.: 3737 Cov.: 32

Gnomad AFR AF: 0.335

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.0340

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.192

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.201

GnomAD4 exome AF: 0.164 AC: 203244 AN: 1237202 Hom.: 17794 Cov.: 31 AF XY: 0.165 AC XY: 98697 AN XY: 597710

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.106

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.0305

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.162

Gnomad4 OTH exome AF: 0.172

GnomAD4 genome AF: 0.206 AC: 31280 AN: 151950 Hom.: 3749 Cov.: 32 AF XY: 0.205 AC XY: 15230 AN XY: 74274

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.0340

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.192

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.199

Alfa AF: 0.168 Hom.: 2150

Bravo AF: 0.206

Asia WGS AF: 0.134 AC: 468 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.51

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs15534; hg19: chr16-55736527;