16-55657912-C-CTCCTGCGGTGCCCGG

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001172501.3(SLC6A2):​c.274+950_274+951insGGTGCCCGGTCCTGC 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: not found (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: AD, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.274+950_274+951insGGTGCCCGGTCCTGC		intron	N/A	NP_001165972.1	P23975-1
	SLC6A2	NM_001172504.1		c.274+950_274+951insGGTGCCCGGTCCTGC		intron	N/A	NP_001165975.1	P23975-2
	SLC6A2	NM_001043.3		c.274+950_274+951insGGTGCCCGGTCCTGC		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.274+944_274+945insTCCTGCGGTGCCCGG		intron	N/A	ENSP00000457473.1	P23975-1
	SLC6A2	ENST00000379906.6	TSL:1	c.274+944_274+945insTCCTGCGGTGCCCGG		intron	N/A	ENSP00000369237.2	P23975-1
	SLC6A2	ENST00000219833.13	TSL:5	c.274+944_274+945insTCCTGCGGTGCCCGG		intron	N/A	ENSP00000219833.8	P23975-2

Frequencies

GnomAD3 genomes Cov.: 0

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

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 665

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.072

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;