chr16-55657912-C-CTCCTGCGGTGCCCAG

Variant names:

• chr16-55657912-C-CTCCTGCGGTGCCCAG
• rs1610905
• NM_001172501.3:c.274+950_274+951insGGTGCCCAGTCCTGC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001172501.3(SLC6A2):​c.274+950_274+951insGGTGCCCAGTCCTGC variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.49 (18729 hom., cov: 0)
• Consequence: SLC6A2 NM_001172501.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• Publications: 6 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.529 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	NM_001172501.3	MANE Select	c.274+950_274+951insGGTGCCCAGTCCTGC		intron	N/A	NP_001165972.1
	SLC6A2	NM_001172504.1		c.274+950_274+951insGGTGCCCAGTCCTGC		intron	N/A	NP_001165975.1
	SLC6A2	NM_001043.3		c.274+950_274+951insGGTGCCCAGTCCTGC		intron	N/A	NP_001034.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000568943.6	TSL:1 MANE Select	c.274+944_274+945insTCCTGCGGTGCCCAG		intron	N/A	ENSP00000457473.1
	SLC6A2	ENST00000379906.6	TSL:1	c.274+944_274+945insTCCTGCGGTGCCCAG		intron	N/A	ENSP00000369237.2
	SLC6A2	ENST00000219833.13	TSL:5	c.274+944_274+945insTCCTGCGGTGCCCAG		intron	N/A	ENSP00000219833.8

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74705 AN: 151704 Hom.: 18722 Cov.: 0

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.589

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.524

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.492 AC: 74747 AN: 151822 Hom.: 18729 Cov.: 0 AF XY: 0.499 AC XY: 37041 AN XY: 74174

African (AFR) AF: 0.395 AC: 16359 AN: 41384

American (AMR) AF: 0.539 AC: 8238 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.484 AC: 1681 AN: 3470

East Asian (EAS) AF: 0.462 AC: 2371 AN: 5130

South Asian (SAS) AF: 0.536 AC: 2575 AN: 4808

European-Finnish (FIN) AF: 0.589 AC: 6198 AN: 10526

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.524 AC: 35622 AN: 67920

Other (OTH) AF: 0.509 AC: 1073 AN: 2108

Alfa AF: 0.328 Hom.: 665

Asia WGS AF: 0.474 AC: 1646 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1610905; hg19: chr16-55691824;