Variant rs5569 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001172501.3(SLC6A2):c.1287G>A(p.Thr429=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 1,613,516 control chromosomes in the GnomAD database, including 88,215 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 6254 hom., cov: 31)

Exomes 𝑓: 0.33 ( 81961 hom. )

Consequence

SLC6A2
NM_001172501.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.10

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 16-55697923-G-A is Benign according to our data. Variant chr16-55697923-G-A is described in ClinVar as [Benign]. Clinvar id is 1283289.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.1 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3 linkuse as main transcript	c.1287G>A	p.Thr429=	synonymous_variant	10/15	ENST00000568943.6	NP_001165972.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6 linkuse as main transcript	c.1287G>A	p.Thr429=	synonymous_variant	10/15	1	NM_001172501.3	ENSP00000457473	P1	P23975-1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

40573

AN:

151886

Hom.:

6249

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.407

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.264

Gnomad EAS

AF:

0.286

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.354

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.335

Gnomad OTH

AF:

0.259

GnomAD3 exomes

AF:

0.313

AC:

78531

AN:

251250

Hom.:

13223

AF XY:

0.308

AC XY:

41781

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.111

Gnomad AMR exome

AF:

0.411

Gnomad ASJ exome

AF:

0.269

Gnomad EAS exome

AF:

0.306

Gnomad SAS exome

AF:

0.198

Gnomad FIN exome

AF:

0.347

Gnomad NFE exome

AF:

0.341

Gnomad OTH exome

AF:

0.291

GnomAD4 exome

AF:

0.329

AC:

480647

AN:

1461512

Hom.:

81961

Cov.:

AF XY:

0.325

AC XY:

236147

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0999

Gnomad4 AMR exome

AF:

0.399

Gnomad4 ASJ exome

AF:

0.273

Gnomad4 EAS exome

AF:

0.273

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.344

Gnomad4 NFE exome

AF:

0.347

Gnomad4 OTH exome

AF:

0.301

GnomAD4 genome

AF:

0.267

AC:

40580

AN:

152004

Hom.:

6254

Cov.:

AF XY:

0.269

AC XY:

19969

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.114

Gnomad4 AMR

AF:

0.332

Gnomad4 ASJ

AF:

0.264

Gnomad4 EAS

AF:

0.286

Gnomad4 SAS

AF:

0.191

Gnomad4 FIN

AF:

0.354

Gnomad4 NFE

AF:

0.335

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.317

Hom.:

12973

Bravo

AF:

0.261

Asia WGS

AF:

0.208

AC:

722

AN:

3478

EpiCase

AF:

0.319

EpiControl

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 28, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.54

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over