rs1443547

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.304G>A(p.Gly102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,604,384 control chromosomes in the GnomAD database, including 102,567 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. G102G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.38 ( 11666 hom., cov: 34)

Exomes 𝑓: 0.35 ( 90901 hom. )

Consequence

SLC6A5
NM_004211.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.24

Publications

25 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=2.0244718E-4).

BP6

Variant 11-20601429-G-A is Benign according to our data. Variant chr11-20601429-G-A is described in ClinVar as Benign. ClinVar VariationId is 304002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.463 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.304G>A	p.Gly102Ser	missense	Exon 2 of 16	NP_004202.4	Q9Y345-1
	SLC6A5	NM_001318369.2		c.-260G>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.304G>A	p.Gly102Ser	missense	Exon 2 of 16	ENSP00000434364.2	Q9Y345-1
	SLC6A5	ENST00000298923.11	TSL:1	n.304G>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000298923.7	J3KNC4

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

58426

AN:

152068

Hom.:

11654

Cov.:

show subpopulations

Gnomad AFR

AF:

0.469

Gnomad AMI

AF:

0.347

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.411

Gnomad EAS

AF:

0.386

Gnomad SAS

AF:

0.442

Gnomad FIN

AF:

0.265

Gnomad MID

AF:

0.414

Gnomad NFE

AF:

0.345

Gnomad OTH

AF:

0.370

GnomAD2 exomes

AF:

0.370

AC:

83572

AN:

226056

AF XY:

0.372

show subpopulations

Gnomad AFR exome

AF:

0.470

Gnomad AMR exome

AF:

0.384

Gnomad ASJ exome

AF:

0.426

Gnomad EAS exome

AF:

0.393

Gnomad FIN exome

AF:

0.266

Gnomad NFE exome

AF:

0.342

Gnomad OTH exome

AF:

0.375

GnomAD4 exome

AF:

0.352

AC:

510646

AN:

1452198

Hom.:

90901

Cov.:

AF XY:

0.354

AC XY:

255810

AN XY:

721666

show subpopulations

African (AFR)

AF:

0.475

AC:

15831

AN:

33332

American (AMR)

AF:

0.382

AC:

16476

AN:

43104

Ashkenazi Jewish (ASJ)

AF:

0.420

AC:

10881

AN:

25900

East Asian (EAS)

AF:

0.389

AC:

15265

AN:

39292

South Asian (SAS)

AF:

0.436

AC:

37076

AN:

85086

European-Finnish (FIN)

AF:

0.267

AC:

13887

AN:

52044

Middle Eastern (MID)

AF:

0.444

AC:

2544

AN:

5726

European-Non Finnish (NFE)

AF:

0.340

AC:

376523

AN:

1107714

Other (OTH)

AF:

0.369

AC:

22163

AN:

60000

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

21808

43616

65423

87231

109039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12278

24556

36834

49112

61390

<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:

0.384

AC:

58448

AN:

152186

Hom.:

11666

Cov.:

AF XY:

0.382

AC XY:

28403

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.468

AC:

19453

AN:

41530

American (AMR)

AF:

0.391

AC:

5976

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.411

AC:

1426

AN:

3472

East Asian (EAS)

AF:

0.385

AC:

1984

AN:

5154

South Asian (SAS)

AF:

0.443

AC:

2140

AN:

4828

European-Finnish (FIN)

AF:

0.265

AC:

2813

AN:

10606

Middle Eastern (MID)

AF:

0.408

AC:

119

AN:

292

European-Non Finnish (NFE)

AF:

0.345

AC:

23432

AN:

67994

Other (OTH)

AF:

0.375

AC:

789

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1883

3766

5648

7531

9414

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

554

1108

1662

2216

2770

<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:

0.354

Hom.:

25770

Bravo

AF:

0.392

TwinsUK

AF:

0.342

AC:

1269

ALSPAC

AF:

0.343

AC:

1322

ESP6500AA

AF:

0.436

AC:

1916

ESP6500EA

AF:

0.335

AC:

2871

ExAC

AF:

0.350

AC:

42097

Asia WGS

AF:

0.442

AC:

1537

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Hyperekplexia 3 (2)

Hyperekplexia (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.014

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.014

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.50

MetaRNN

Benign

0.00020

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PhyloP100

-2.2

PrimateAI

Benign

0.45

PROVEAN

Benign

0.26

REVEL

Benign

0.049

Sift

Benign

0.72

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.018

MPC

0.19

ClinPred

0.00087

GERP RS

-4.0

Varity_R

0.033

gMVP

0.25

Mutation Taster

=93/7

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