16-55707544-T-C

Position:

• chr16-55707544-T-C

Variant summary

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

The ENST00000682050.1(SLC6A2):​c.*5751T>C 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 0.158 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 3_prime_UTR, NMD_transcript
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A2	ENST00000682050.1	c.*5751T>C		3_prime_UTR_variant, NMD_transcript_variant	13/13

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;