rs1345429

Variant names:

• chr16-55688938-A-G
• rs1345429
• NM_001172501.3:c.784-2980A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-55688938-A-G
• chr16-55688938-A-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.784-2980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 151,994 control chromosomes in the GnomAD database, including 16,121 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 0.45 (16121 hom., cov: 32)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.341
• Publications: 4 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=-0.74).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3	c.784-2980A>G		intron_variant	Intron 5 of 14	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6	c.784-2980A>G		intron_variant	Intron 5 of 14	1	NM_001172501.3	ENSP00000457473.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68888 AN: 151876 Hom.: 16116 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.492

Gnomad ASJ AF: 0.575

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.475

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.453 AC: 68911 AN: 151994 Hom.: 16121 Cov.: 32 AF XY: 0.456 AC XY: 33842 AN XY: 74276

African (AFR) AF: 0.344 AC: 14249 AN: 41418

American (AMR) AF: 0.492 AC: 7507 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.575 AC: 1996 AN: 3472

East Asian (EAS) AF: 0.705 AC: 3638 AN: 5162

South Asian (SAS) AF: 0.540 AC: 2594 AN: 4808

European-Finnish (FIN) AF: 0.475 AC: 5022 AN: 10576

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.476 AC: 32353 AN: 67968

Other (OTH) AF: 0.486 AC: 1026 AN: 2112

Alfa AF: 0.475 Hom.: 29178

Bravo AF: 0.453

Asia WGS AF: 0.599 AC: 2082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	2.5
DANN	Benign	0.81
PhyloP100		0.34
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: rs1345429; hg19: chr16-55722850;