Variant 16-55694046-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BS1BS2

The NM_001172501.3(SLC6A2):c.955T>C(p.Leu319Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,613,572 control chromosomes in the GnomAD database, including 356 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 0.013 ( 32 hom., cov: 33)

Exomes 𝑓: 0.018 ( 324 hom. )

Consequence

SLC6A2
NM_001172501.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.225

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP7

Synonymous conserved (PhyloP=0.225 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0135 (2055/152286) while in subpopulation NFE AF= 0.0202 (1371/68016). AF 95% confidence interval is 0.0193. There are 32 homozygotes in gnomad4. There are 1081 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2055 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A2	NM_001172501.3 linkuse as main transcript	c.955T>C	p.Leu319Leu	synonymous_variant	7/15	ENST00000568943.6	NP_001165972.1	P23975-1A0A024R6T9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A2	ENST00000568943.6 linkuse as main transcript	c.955T>C	p.Leu319Leu	synonymous_variant	7/15	1	NM_001172501.3	ENSP00000457473.1		P23975-1

Frequencies

GnomAD3 genomes

AF:

0.0135

AC:

2054

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00302

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00726

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0362

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0202

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.0134

AC:

3361

AN:

251478

Hom.:

AF XY:

0.0135

AC XY:

1835

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.00369

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.00625

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00346

Gnomad FIN exome

AF:

0.0344

Gnomad NFE exome

AF:

0.0194

Gnomad OTH exome

AF:

0.00961

GnomAD4 exome

AF:

0.0184

AC:

26885

AN:

1461286

Hom.:

324

Cov.:

AF XY:

0.0180

AC XY:

13079

AN XY:

727016

show subpopulations

Gnomad4 AFR exome

AF:

0.00320

Gnomad4 AMR exome

AF:

0.00367

Gnomad4 ASJ exome

AF:

0.00608

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.0212

Gnomad4 OTH exome

AF:

0.0133

GnomAD4 genome

AF:

0.0135

AC:

2055

AN:

152286

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1081

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00301

Gnomad4 AMR

AF:

0.00725

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0362

Gnomad4 NFE

AF:

0.0202

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0111

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.1

DANN

Benign

0.65

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over