dbSNP rs2272400: SLC6A11:p.Cys524Cys (chr3-10934163-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_014229.3(SLC6A11):c.1572C>T(p.Cys524Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0148 in 1,608,836 control chromosomes in the GnomAD database, including 944 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 0.015 ( 83 hom., cov: 32)

Exomes 𝑓: 0.015 ( 861 hom. )

Consequence

SLC6A11
NM_014229.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

14 publications found

Variant links:

Genes affected

SLC6A11 (HGNC:11044): (solute carrier family 6 member 11) The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

SLC6A11 links:

ENSG00000286962 (HGNC:):

ENSG00000286962 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP7

Synonymous conserved (PhyloP=-0.457 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3 link	c.1572C>T	p.Cys524Cys	synonymous_variant	Exon 12 of 14	ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1 link	c.1050C>T	p.Cys350Cys	synonymous_variant	Exon 10 of 12		XP_047304720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SLC6A11	ENST00000254488.7 link	c.1572C>T	p.Cys524Cys	synonymous_variant	Exon 12 of 14	1	NM_014229.3	ENSP00000254488.2
SLC6A11	ENST00000464828.1 link	n.198C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3
ENSG00000286962	ENST00000656787.1 link	n.350+2827G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2315

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00915

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00667

Gnomad ASJ

AF:

0.00980

Gnomad EAS

AF:

0.163

Gnomad SAS

AF:

0.0638

Gnomad FIN

AF:

0.00914

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00770

Gnomad OTH

AF:

0.0120

GnomAD2 exomes

AF:

0.0258

AC:

6472

AN:

251082

AF XY:

0.0264

show subpopulations

Gnomad AFR exome

AF:

0.00867

Gnomad AMR exome

AF:

0.00819

Gnomad ASJ exome

AF:

0.00814

Gnomad EAS exome

AF:

0.170

Gnomad FIN exome

AF:

0.00828

Gnomad NFE exome

AF:

0.00726

Gnomad OTH exome

AF:

0.0170

GnomAD4 exome

AF:

0.0148

AC:

21548

AN:

1456586

Hom.:

861

Cov.:

AF XY:

0.0161

AC XY:

11650

AN XY:

725008

show subpopulations

African (AFR)

AF:

0.00731

AC:

244

AN:

33382

American (AMR)

AF:

0.00767

AC:

343

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00897

AC:

234

AN:

26100

East Asian (EAS)

AF:

0.176

AC:

6984

AN:

39652

South Asian (SAS)

AF:

0.0564

AC:

4854

AN:

86098

European-Finnish (FIN)

AF:

0.00877

AC:

468

AN:

53390

Middle Eastern (MID)

AF:

0.00886

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00653

AC:

7230

AN:

1107288

Other (OTH)

AF:

0.0189

AC:

1140

AN:

60210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

889

1778

2668

3557

4446

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.0151

AC:

2306

AN:

152250

Hom.:

Cov.:

AF XY:

0.0169

AC XY:

1257

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00917

AC:

381

AN:

41546

American (AMR)

AF:

0.00667

AC:

102

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00980

AC:

AN:

3468

East Asian (EAS)

AF:

0.162

AC:

839

AN:

5174

South Asian (SAS)

AF:

0.0630

AC:

304

AN:

4824

European-Finnish (FIN)

AF:

0.00914

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00771

AC:

524

AN:

68004

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

114

228

343

457

571

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

144

180

<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:

0.0104

Hom.:

107

Bravo

AF:

0.0147

Asia WGS

AF:

0.120

AC:

417

AN:

3478

EpiCase

AF:

0.00710

EpiControl

AF:

0.00729

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.3

(source)

DANN

Benign

0.78

PhyloP100

-0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over