Genetic Variant NM_014229.3:c.645T>C (chr3-10844235-T-C) – 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.645T>C(p.Ser215Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,613,944 control chromosomes in the GnomAD database, including 93,608 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 0.33 ( 8399 hom., cov: 33)

Exomes 𝑓: 0.34 ( 85209 hom. )

Consequence

SLC6A11
NM_014229.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -6.71

Publications

28 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:

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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=-0.92).

BP7

Synonymous conserved (PhyloP=-6.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3 link	c.645T>C	p.Ser215Ser	synonymous_variant	Exon 5 of 14	ENST00000254488.7	NP_055044.1	P48066-1
SLC6A11	XM_047448764.1 link	c.123T>C	p.Ser41Ser	synonymous_variant	Exon 3 of 12		XP_047304720.1
SLC6A11	XM_011534033.3 link	c.645T>C	p.Ser215Ser	synonymous_variant	Exon 5 of 9		XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7 link	c.645T>C	p.Ser215Ser	synonymous_variant	Exon 5 of 14	1	NM_014229.3	ENSP00000254488.2		P48066-1

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49706

AN:

152040

Hom.:

8394

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.235

Gnomad ASJ

AF:

0.407

Gnomad EAS

AF:

0.436

Gnomad SAS

AF:

0.509

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.399

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.325

GnomAD2 exomes

AF:

0.341

AC:

85716

AN:

251176

AF XY:

0.354

show subpopulations

Gnomad AFR exome

AF:

0.319

Gnomad AMR exome

AF:

0.181

Gnomad ASJ exome

AF:

0.407

Gnomad EAS exome

AF:

0.458

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.329

Gnomad OTH exome

AF:

0.344

GnomAD4 exome

AF:

0.337

AC:

492583

AN:

1461786

Hom.:

85209

Cov.:

AF XY:

0.343

AC XY:

249412

AN XY:

727198

show subpopulations

African (AFR)

AF:

0.321

AC:

10730

AN:

33476

American (AMR)

AF:

0.188

AC:

8387

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.402

AC:

10496

AN:

26132

East Asian (EAS)

AF:

0.418

AC:

16591

AN:

39700

South Asian (SAS)

AF:

0.502

AC:

43282

AN:

86250

European-Finnish (FIN)

AF:

0.309

AC:

16518

AN:

53410

Middle Eastern (MID)

AF:

0.424

AC:

2444

AN:

5768

European-Non Finnish (NFE)

AF:

0.326

AC:

362448

AN:

1111934

Other (OTH)

AF:

0.359

AC:

21687

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

17903

35806

53708

71611

89514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11936

23872

35808

47744

59680

<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:

0.327

AC:

49731

AN:

152158

Hom.:

8399

Cov.:

AF XY:

0.329

AC XY:

24506

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.321

AC:

13308

AN:

41496

American (AMR)

AF:

0.235

AC:

3593

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.407

AC:

1413

AN:

3472

East Asian (EAS)

AF:

0.436

AC:

2252

AN:

5168

South Asian (SAS)

AF:

0.510

AC:

2455

AN:

4814

European-Finnish (FIN)

AF:

0.309

AC:

3269

AN:

10592

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.327

AC:

22209

AN:

68004

Other (OTH)

AF:

0.324

AC:

685

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1742

3484

5226

6968

8710

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

498

996

1494

1992

2490

<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:

0.333

Hom.:

42440

Bravo

AF:

0.319

Asia WGS

AF:

0.456

AC:

1589

AN:

3478

EpiCase

AF:

0.344

EpiControl

AF:

0.343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.64

(source)

DANN

Benign

0.40

PhyloP100

-6.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=99/1

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

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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