16-55707385-T-G

Variant summary

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

The ENST00000682050.1(SLC6A2):c.*5592T>G variant causes a 3 prime UTR, NMD transcript 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 3_prime_UTR, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.341

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 = 0.349 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000682050.1	c.*5592T>G		3_prime_UTR_variant, NMD_transcript_variant	13/13

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

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.0313

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.286

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.239

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
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: rs9930182; hg19: chr16-55741297;