rs16955708

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000682050.1	n.*5751T>C		non_coding_transcript_exon_variant	Exon 13 of 13			ENSP00000508367.1
SLC6A2	ENST00000682050.1	n.*5751T>C		3_prime_UTR_variant	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

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.153

Gnomad4 EAS AF: 0.0301

Gnomad4 SAS AF: 0.0956

Gnomad4 FIN AF: 0.208

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.151

Alfa AF: 0.153 Hom.: 2547

Bravo AF: 0.154

Asia WGS AF: 0.0760 AC: 267 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16955708; hg19: chr16-55741456;