16-55656513-C-T

Position:

• chr16-55656513-C-T

Variant summary

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

The ENST00000379906.6(SLC6A2):​c.-182C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.726 in 723,068 control chromosomes in the GnomAD database, including 190,945 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 0.75 (42358 hom., cov: 30)
  • Exomes 𝑓: 0.72 (148587 hom.)
• Consequence: SLC6A2 ENST00000379906.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.247

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=-0.71).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.-51-131C>T		intron_variant		ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.-51-131C>T		intron_variant		1	NM_001172501.3	ENSP00000457473	P1

Frequencies

GnomAD3 genomes AF: 0.746 AC: 113047 AN: 151628 Hom.: 42319 Cov.: 30

Gnomad AFR AF: 0.812

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.684

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.737

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.715

Gnomad OTH AF: 0.730

GnomAD4 exome AF: 0.720 AC: 411532 AN: 571322 Hom.: 148587 Cov.: 7 AF XY: 0.720 AC XY: 216804 AN XY: 301178

Gnomad4 AFR exome AF: 0.806

Gnomad4 AMR exome AF: 0.762

Gnomad4 ASJ exome AF: 0.702

Gnomad4 EAS exome AF: 0.660

Gnomad4 SAS exome AF: 0.731

Gnomad4 FIN exome AF: 0.723

Gnomad4 NFE exome AF: 0.719

Gnomad4 OTH exome AF: 0.721

GnomAD4 genome AF: 0.746 AC: 113151 AN: 151746 Hom.: 42358 Cov.: 30 AF XY: 0.749 AC XY: 55496 AN XY: 74140

Gnomad4 AFR AF: 0.812

Gnomad4 AMR AF: 0.753

Gnomad4 ASJ AF: 0.706

Gnomad4 EAS AF: 0.682

Gnomad4 SAS AF: 0.727

Gnomad4 FIN AF: 0.737

Gnomad4 NFE AF: 0.715

Gnomad4 OTH AF: 0.733

Alfa AF: 0.717 Hom.: 76876

Bravo AF: 0.749

Asia WGS AF: 0.704 AC: 2448 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.7
DANN	Benign	0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2242446; hg19: chr16-55690425;