Variant rs2000959 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004211.5(SLC6A5):c.1738-39C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 1,606,736 control chromosomes in the GnomAD database, including 89,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7409 hom., cov: 30)

Exomes 𝑓: 0.33 ( 82456 hom. )

Consequence

SLC6A5
NM_004211.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.07

Variant links:

Genes affected

SLC6A5 (HGNC:11051): (solute carrier family 6 member 5) This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

SLC6A5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 11-20637133-C-A is Benign according to our data. Variant chr11-20637133-C-A is described in ClinVar as [Benign]. Clinvar id is 1294497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
SLC6A5	NM_004211.5 linkuse as main transcript	c.1738-39C>A	intron_variant	ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2 linkuse as main transcript	c.1036-39C>A	intron_variant		NP_001305298.1
SLC6A5	XM_017018544.3 linkuse as main transcript	c.862-39C>A	intron_variant		XP_016874033.1
SLC6A5	XR_007062528.1 linkuse as main transcript	n.1116-39C>A	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6 linkuse as main transcript	c.1738-39C>A	intron_variant	1	NM_004211.5	ENSP00000434364	P1	Q9Y345-1
SLC6A5	ENST00000298923.11 linkuse as main transcript	c.*1035-39C>A	intron_variant, NMD_transcript_variant	1		ENSP00000298923
SLC6A5	ENST00000528440.1 linkuse as main transcript	n.269-39C>A	intron_variant, non_coding_transcript_variant	5

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45277

AN:

151666

Hom.:

7389

Cov.:

show subpopulations

Gnomad AFR

AF:

0.176

Gnomad AMI

AF:

0.321

Gnomad AMR

AF:

0.422

Gnomad ASJ

AF:

0.380

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.496

Gnomad FIN

AF:

0.332

Gnomad MID

AF:

0.293

Gnomad NFE

AF:

0.317

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.366

AC:

91911

AN:

251264

Hom.:

18353

AF XY:

0.369

AC XY:

50093

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.550

Gnomad ASJ exome

AF:

0.380

Gnomad EAS exome

AF:

0.354

Gnomad SAS exome

AF:

0.491

Gnomad FIN exome

AF:

0.329

Gnomad NFE exome

AF:

0.312

Gnomad OTH exome

AF:

0.354

GnomAD4 exome

AF:

0.329

AC:

478604

AN:

1454954

Hom.:

82456

Cov.:

AF XY:

0.334

AC XY:

242161

AN XY:

724206

show subpopulations

Gnomad4 AFR exome

AF:

0.168

Gnomad4 AMR exome

AF:

0.534

Gnomad4 ASJ exome

AF:

0.382

Gnomad4 EAS exome

AF:

0.381

Gnomad4 SAS exome

AF:

0.493

Gnomad4 FIN exome

AF:

0.328

Gnomad4 NFE exome

AF:

0.310

Gnomad4 OTH exome

AF:

0.329

GnomAD4 genome

AF:

0.299

AC:

45310

AN:

151782

Hom.:

7409

Cov.:

AF XY:

0.307

AC XY:

22739

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.176

Gnomad4 AMR

AF:

0.423

Gnomad4 ASJ

AF:

0.380

Gnomad4 EAS

AF:

0.359

Gnomad4 SAS

AF:

0.497

Gnomad4 FIN

AF:

0.332

Gnomad4 NFE

AF:

0.317

Gnomad4 OTH

AF:

0.316

Alfa

AF:

0.320

Hom.:

16456

Bravo

AF:

0.297

Asia WGS

AF:

0.440

AC:

1529

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

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	Aug 22, 2019	- -

Hyperekplexia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.033

DANN

Benign

0.49

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