ENST00000682050.1:n.*5592T>G

Variant names:

• chr16-55707385-T-G
• rs9930182
• ENST00000682050.1:n.*5592T>G

Variant summary

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

The ENST00000682050.1(SLC6A2):​n.*5592T>G 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 0.251 in 151,962 control chromosomes in the GnomAD database, including 5,226 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 0.25 (5226 hom., cov: 31)
• Consequence: SLC6A2 ENST00000682050.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341
• Publications: 2 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 = 0.349 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000682050.1		n.*5592T>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000508367.1
	SLC6A2	ENST00000682050.1		n.*5592T>G		3_prime_UTR	Exon 13 of 13	ENSP00000508367.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38033 AN: 151844 Hom.: 5212 Cov.: 31

Gnomad AFR AF: 0.353

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.0313

Gnomad SAS AF: 0.216

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.240

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

GnomAD4 genome AF: 0.251 AC: 38095 AN: 151962 Hom.: 5226 Cov.: 31 AF XY: 0.251 AC XY: 18626 AN XY: 74294

African (AFR) AF: 0.354 AC: 14651 AN: 41406

American (AMR) AF: 0.165 AC: 2524 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 757 AN: 3466

East Asian (EAS) AF: 0.0313 AC: 162 AN: 5168

South Asian (SAS) AF: 0.217 AC: 1043 AN: 4806

European-Finnish (FIN) AF: 0.286 AC: 3025 AN: 10580

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15088 AN: 67938

Other (OTH) AF: 0.239 AC: 504 AN: 2110

Alfa AF: 0.130 Hom.: 240

Bravo AF: 0.246

Asia WGS AF: 0.141 AC: 494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.51
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs9930182; hg19: chr16-55741297;