rs61736603

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004211.5(SLC6A5):c.500C>A(p.Thr167Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00325 in 1,614,056 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T167T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.017 ( 93 hom., cov: 33)

Exomes 𝑓: 0.0018 ( 94 hom. )

Consequence

SLC6A5
NM_004211.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.63

Publications

4 publications found

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 Gene-Disease associations (from GenCC):

hyperekplexia 3
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, PanelApp Australia
hereditary hyperekplexia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC6A5 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003014952).

BP6

Variant 11-20601625-C-A is Benign according to our data. Variant chr11-20601625-C-A is described in ClinVar as Benign. ClinVar VariationId is 304012.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0575 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004211.5. 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
	SLC6A5	NM_004211.5	MANE Select	c.500C>A	p.Thr167Lys	missense	Exon 2 of 16	NP_004202.4	Q9Y345-1
	SLC6A5	NM_001318369.2		c.-64C>A		5_prime_UTR	Exon 2 of 15	NP_001305298.1	Q9Y345-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A5	ENST00000525748.6	TSL:1 MANE Select	c.500C>A	p.Thr167Lys	missense	Exon 2 of 16	ENSP00000434364.2	Q9Y345-1
	SLC6A5	ENST00000298923.11	TSL:1	n.500C>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000298923.7	J3KNC4

Frequencies

GnomAD3 genomes

AF:

0.0170

AC:

2594

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0595

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00463

AC:

1153

AN:

248834

AF XY:

0.00358

show subpopulations

Gnomad AFR exome

AF:

0.0636

Gnomad AMR exome

AF:

0.00261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000188

Gnomad OTH exome

AF:

0.00115

GnomAD4 exome

AF:

0.00180

AC:

2638

AN:

1461732

Hom.:

Cov.:

AF XY:

0.00158

AC XY:

1149

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.0646

AC:

2164

AN:

33474

American (AMR)

AF:

0.00277

AC:

124

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.000255

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53366

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000755

AC:

AN:

1111950

Other (OTH)

AF:

0.00383

AC:

231

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

151

302

453

604

755

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0171

AC:

2601

AN:

152324

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1232

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0595

AC:

2473

AN:

41568

American (AMR)

AF:

0.00575

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68026

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

123

246

370

493

616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

140

<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:

0.00389

Hom.:

Bravo

AF:

0.0196

ESP6500AA

AF:

0.0626

AC:

276

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00572

AC:

695

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperekplexia (1)

Hyperekplexia 3 (1)

not provided (1)

SLC6A5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.27

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.86

MetaRNN

Benign

0.0030

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

PhyloP100

5.6

PrimateAI

Benign

0.47

PROVEAN

Benign

-0.56

REVEL

Benign

0.29

Sift

Benign

0.16

Sift4G

Benign

0.13

Polyphen

0.55

Vest4

0.43

MVP

0.87

MPC

0.29

ClinPred

0.045

GERP RS

5.4

Varity_R

0.22

gMVP

0.57

Mutation Taster

=69/31

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over