rs11568324

Variant names:

• chr16-55692146-C-T
• rs11568324
• NM_001172501.3:c.918+94C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001172501.3(SLC6A2):​c.918+94C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.008 in 1,403,994 control chromosomes in the GnomAD database, including 90 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 0.0053 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0083 (80 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.458
• Publications: 13 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 811 AD,Unknown gene.

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.918+94C>T		intron	N/A	NP_001165972.1	P23975-1
	SLC6A2	NM_001172504.1		c.918+94C>T		intron	N/A	NP_001165975.1	P23975-2
	SLC6A2	NM_001043.3		c.918+94C>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.918+94C>T		intron	N/A	ENSP00000457473.1	P23975-1
	SLC6A2	ENST00000379906.6	TSL:1	c.918+94C>T		intron	N/A	ENSP00000369237.2	P23975-1
	SLC6A2	ENST00000219833.13	TSL:5	c.918+94C>T		intron	N/A	ENSP00000219833.8	P23975-2

Frequencies

GnomAD3 genomes AF: 0.00533 AC: 811 AN: 152196 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00559

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00848

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.00832 AC: 10418 AN: 1251680 Hom.: 80 AF XY: 0.00835 AC XY: 5290 AN XY: 633496

African (AFR) AF: 0.00135 AC: 40 AN: 29542

American (AMR) AF: 0.00268 AC: 119 AN: 44398

Ashkenazi Jewish (ASJ) AF: 0.000966 AC: 24 AN: 24846

East Asian (EAS) AF: 0.0000259 AC: 1 AN: 38670

South Asian (SAS) AF: 0.00653 AC: 533 AN: 81632

European-Finnish (FIN) AF: 0.00655 AC: 315 AN: 48088

Middle Eastern (MID) AF: 0.00518 AC: 28 AN: 5402

European-Non Finnish (NFE) AF: 0.00966 AC: 8945 AN: 925642

Other (OTH) AF: 0.00773 AC: 413 AN: 53460

GnomAD4 genome AF: 0.00532 AC: 811 AN: 152314 Hom.: 10 Cov.: 32 AF XY: 0.00510 AC XY: 380 AN XY: 74470

African (AFR) AF: 0.00180 AC: 75 AN: 41578

American (AMR) AF: 0.00275 AC: 42 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4826

European-Finnish (FIN) AF: 0.00612 AC: 65 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00848 AC: 577 AN: 68040

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.00750 Hom.: 2

Bravo AF: 0.00479

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.71
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism

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: rs11568324; hg19: chr16-55726058;