Genetic Variant SLC6A2:n.*5592T>G (chr16-55707385-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000682050.1(SLC6A2):n.*5592T>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.251 in 151,962 control chromosomes in the GnomAD database, including 5,226 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 0.25 ( 5226 hom., cov: 31)

Consequence

SLC6A2
ENST00000682050.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.341

Publications

2 publications found

Variant links:

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), PanelApp Australia, Orphanet

SLC6A2 links:

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new If you want to explore the variant's impact on the transcript ENST00000682050.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.349 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000682050.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A2	ENST00000682050.1		n.*5592T>G		non_coding_transcript_exon	Exon 13 of 13	ENSP00000508367.1	A0A804HLI4
	SLC6A2	ENST00000682050.1		n.*5592T>G		3_prime_UTR	Exon 13 of 13	ENSP00000508367.1	A0A804HLI4

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38033

AN:

151844

Hom.:

5212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.292

Gnomad AMR

AF:

0.165

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.0313

Gnomad SAS

AF:

0.216

Gnomad FIN

AF:

0.286

Gnomad MID

AF:

0.259

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.240

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

GnomAD4 genome

AF:

0.251

AC:

38095

AN:

151962

Hom.:

5226

Cov.:

AF XY:

0.251

AC XY:

18626

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.354

AC:

14651

AN:

41406

American (AMR)

AF:

0.165

AC:

2524

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

757

AN:

3466

East Asian (EAS)

AF:

0.0313

AC:

162

AN:

5168

South Asian (SAS)

AF:

0.217

AC:

1043

AN:

4806

European-Finnish (FIN)

AF:

0.286

AC:

3025

AN:

10580

Middle Eastern (MID)

AF:

0.259

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15088

AN:

67938

Other (OTH)

AF:

0.239

AC:

504

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1376

2752

4127

5503

6879

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.130

Hom.:

240

Bravo

AF:

0.246

Asia WGS

AF:

0.141

AC:

494

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

(source)

DANN

Benign

0.51

PhyloP100

-0.34

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over