Genetic Variant SLC6A2:c.*1433C>T (chr16-55703779-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001172501.3(SLC6A2):c.*1433C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 984,876 control chromosomes in the GnomAD database, including 15,964 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 0.21 ( 3861 hom., cov: 32)

Exomes 𝑓: 0.17 ( 12103 hom. )

Consequence

SLC6A2
NM_001172501.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.882

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A2	NM_001172501.3 link	c.*1433C>T		3_prime_UTR_variant	Exon 15 of 15	ENST00000568943.6	NP_001165972.1	P23975-1A0A024R6T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6 link	c.*1433C>T		3_prime_UTR_variant	Exon 15 of 15	1	NM_001172501.3	ENSP00000457473.1		P23975-1

Frequencies

GnomAD3 genomes

AF:

0.208

AC:

31620

AN:

151922

Hom.:

3848

Cov.:

show subpopulations

Gnomad AFR

AF:

0.342

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.130

Gnomad ASJ

AF:

0.157

Gnomad EAS

AF:

0.0338

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.203

GnomAD4 exome

AF:

0.167

AC:

139219

AN:

832836

Hom.:

12103

Cov.:

AF XY:

0.168

AC XY:

64461

AN XY:

384598

show subpopulations

Gnomad4 AFR exome

AF:

0.361

Gnomad4 AMR exome

AF:

0.0894

Gnomad4 ASJ exome

AF:

0.157

Gnomad4 EAS exome

AF:

0.0440

Gnomad4 SAS exome

AF:

0.193

Gnomad4 FIN exome

AF:

0.185

Gnomad4 NFE exome

AF:

0.163

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.208

AC:

31678

AN:

152040

Hom.:

3861

Cov.:

AF XY:

0.207

AC XY:

15412

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.342

Gnomad4 AMR

AF:

0.130

Gnomad4 ASJ

AF:

0.157

Gnomad4 EAS

AF:

0.0339

Gnomad4 SAS

AF:

0.202

Gnomad4 FIN

AF:

0.193

Gnomad4 NFE

AF:

0.163

Gnomad4 OTH

AF:

0.201

Alfa

AF:

0.158

Hom.:

3511

Bravo

AF:

0.209

Asia WGS

AF:

0.133

AC:

465

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.66

DANN

Benign

0.57

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over