rs36010

Positions:

• chr16-55697756-C-A

Variant summary

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

The NM_001172501.3(SLC6A2):​c.1261-141C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0503 in 781,954 control chromosomes in the GnomAD database, including 2,489 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 0.075 (845 hom., cov: 32)
  • Exomes 𝑓: 0.044 (1644 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.1261-141C>A		intron_variant		ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.1261-141C>A		intron_variant		1	NM_001172501.3	ENSP00000457473	P1

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11352 AN: 152022 Hom.: 846 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0687

Gnomad ASJ AF: 0.0303

Gnomad EAS AF: 0.256

Gnomad SAS AF: 0.0824

Gnomad FIN AF: 0.0157

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0741

GnomAD4 exome AF: 0.0444 AC: 27966 AN: 629812 Hom.: 1644 AF XY: 0.0449 AC XY: 14839 AN XY: 330636

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.0690

Gnomad4 ASJ exome AF: 0.0302

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.0790

Gnomad4 FIN exome AF: 0.0190

Gnomad4 NFE exome AF: 0.0193

Gnomad4 OTH exome AF: 0.0488

GnomAD4 genome AF: 0.0747 AC: 11362 AN: 152142 Hom.: 845 Cov.: 32 AF XY: 0.0757 AC XY: 5633 AN XY: 74374

Gnomad4 AFR AF: 0.163

Gnomad4 AMR AF: 0.0684

Gnomad4 ASJ AF: 0.0303

Gnomad4 EAS AF: 0.255

Gnomad4 SAS AF: 0.0822

Gnomad4 FIN AF: 0.0157

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0483 Hom.: 45

Bravo AF: 0.0841

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.81
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs36010; hg19: chr16-55731668;