16-55698708-C-T

Variant names:

• chr16-55698708-C-T
• rs36009
• NM_001172501.3:c.1489+140C>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.1489+140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0877 in 712,680 control chromosomes in the GnomAD database, including 2,991 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 0.080 (516 hom., cov: 32)
  • Exomes 𝑓: 0.090 (2475 hom.)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.248
• Publications: 12 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: Unknown, AD Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.1489+140C>T		intron_variant	Intron 11 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.1489+140C>T		intron_variant	Intron 11 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.0803 AC: 12214 AN: 152094 Hom.: 516 Cov.: 32

Gnomad AFR AF: 0.0556

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0673

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0904

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.0856

GnomAD4 exome AF: 0.0897 AC: 50271 AN: 560468 Hom.: 2475 AF XY: 0.0903 AC XY: 27293 AN XY: 302336

African (AFR) AF: 0.0522 AC: 801 AN: 15336

American (AMR) AF: 0.0652 AC: 2167 AN: 33252

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 1147 AN: 19220

East Asian (EAS) AF: 0.167 AC: 5356 AN: 32016

South Asian (SAS) AF: 0.0978 AC: 5937 AN: 60692

European-Finnish (FIN) AF: 0.109 AC: 4969 AN: 45670

Middle Eastern (MID) AF: 0.0870 AC: 211 AN: 2426

European-Non Finnish (NFE) AF: 0.0837 AC: 26926 AN: 321652

Other (OTH) AF: 0.0913 AC: 2757 AN: 30204

GnomAD4 genome AF: 0.0802 AC: 12211 AN: 152212 Hom.: 516 Cov.: 32 AF XY: 0.0823 AC XY: 6122 AN XY: 74426

African (AFR) AF: 0.0553 AC: 2299 AN: 41542

American (AMR) AF: 0.0671 AC: 1026 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.168 AC: 867 AN: 5156

South Asian (SAS) AF: 0.0905 AC: 436 AN: 4818

European-Finnish (FIN) AF: 0.109 AC: 1154 AN: 10598

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0860 AC: 5852 AN: 68020

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0835 Hom.: 966

Bravo AF: 0.0775

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.7
DANN	Benign	0.59
PhyloP100		-0.25
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: rs36009; hg19: chr16-55732620;