rs16955708

Variant names:

• chr16-55707544-T-C
• rs16955708
• ENST00000682050.1:n.*5751T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000682050.1(SLC6A2):​n.*5751T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 152,164 control chromosomes in the GnomAD database, including 2,019 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 0.16 (2019 hom., cov: 32)
• Consequence: SLC6A2 ENST00000682050.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.408
• Publications: 7 publications found

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]

SLC6A2 Gene-Disease associations (from GenCC):

• postural orthostatic tachycardia syndrome

  Inheritance: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682050.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000682050.1		n.*5751T>C		non_coding_transcript_exon	Exon 13 of 13	ENSP00000508367.1
	SLC6A2	ENST00000682050.1		n.*5751T>C		3_prime_UTR	Exon 13 of 13	ENSP00000508367.1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 24059 AN: 152046 Hom.: 2017 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.153

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0955

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.158 AC: 24083 AN: 152164 Hom.: 2019 Cov.: 32 AF XY: 0.159 AC XY: 11825 AN XY: 74392

African (AFR) AF: 0.185 AC: 7671 AN: 41504

American (AMR) AF: 0.116 AC: 1775 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.153 AC: 529 AN: 3464

East Asian (EAS) AF: 0.0301 AC: 156 AN: 5180

South Asian (SAS) AF: 0.0956 AC: 461 AN: 4822

European-Finnish (FIN) AF: 0.208 AC: 2198 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10778 AN: 67998

Other (OTH) AF: 0.151 AC: 319 AN: 2106

Alfa AF: 0.152 Hom.: 3493

Bravo AF: 0.154

Asia WGS AF: 0.0760 AC: 267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	0.68
PhyloP100		-0.41

Splicing

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

Other links and lift over

dbSNP: rs16955708; hg19: chr16-55741456;