NM_001172501.3:c.784-1888C>T

Variant names:

• chr16-55690030-C-T
• rs11862589
• NM_001172501.3:c.784-1888C>T

Variant summary

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

The NM_001172501.3(SLC6A2):​c.784-1888C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.475 in 152,018 control chromosomes in the GnomAD database, including 17,334 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 0.47 (17334 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 8 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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172501.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	NM_001172501.3	MANE Select	c.784-1888C>T		intron	N/A	NP_001165972.1	P23975-1
	SLC6A2	NM_001172504.1		c.784-1888C>T		intron	N/A	NP_001165975.1	P23975-2
	SLC6A2	NM_001043.3		c.784-1888C>T		intron	N/A	NP_001034.1	P23975-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000568943.6	TSL:1 MANE Select	c.784-1888C>T		intron	N/A	ENSP00000457473.1	P23975-1
	SLC6A2	ENST00000379906.6	TSL:1	c.784-1888C>T		intron	N/A	ENSP00000369237.2	P23975-1
	SLC6A2	ENST00000219833.13	TSL:5	c.784-1888C>T		intron	N/A	ENSP00000219833.8	P23975-2

Frequencies

GnomAD3 genomes AF: 0.475 AC: 72120 AN: 151900 Hom.: 17323 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.434

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.475 AC: 72153 AN: 152018 Hom.: 17334 Cov.: 32 AF XY: 0.476 AC XY: 35399 AN XY: 74296

African (AFR) AF: 0.419 AC: 17357 AN: 41450

American (AMR) AF: 0.499 AC: 7635 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3470

East Asian (EAS) AF: 0.703 AC: 3632 AN: 5166

South Asian (SAS) AF: 0.540 AC: 2603 AN: 4820

European-Finnish (FIN) AF: 0.475 AC: 5017 AN: 10562

Middle Eastern (MID) AF: 0.435 AC: 127 AN: 292

European-Non Finnish (NFE) AF: 0.476 AC: 32340 AN: 67954

Other (OTH) AF: 0.499 AC: 1051 AN: 2108

Alfa AF: 0.479 Hom.: 10279

Bravo AF: 0.477

Asia WGS AF: 0.608 AC: 2112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.45
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11862589; hg19: chr16-55723942;