chr11-20601477-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004211.5(SLC6A5):c.352C>T(p.Leu118Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,611,814 control chromosomes in the GnomAD database, including 90,109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.32 ( 8118 hom., cov: 34)

Exomes 𝑓: 0.33 ( 81991 hom. )

Consequence

SLC6A5
NM_004211.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.752

Publications

19 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 Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 11-20601477-C-T is Benign according to our data. Variant chr11-20601477-C-T is described in CliVar as Benign. Clinvar id is 304006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-20601477-C-T is described in CliVar as Benign. Clinvar id is 304006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-20601477-C-T is described in CliVar as Benign. Clinvar id is 304006.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.752 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A5	NM_004211.5 link	c.352C>T	p.Leu118Leu	synonymous_variant	Exon 2 of 16	ENST00000525748.6	NP_004202.4	Q9Y345-1Q4VAM4Q4VAM6
SLC6A5	NM_001318369.2 link	c.-212C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 2 of 15		NP_001305298.1	Q9Y345-2Q4VAM4
SLC6A5	NM_001318369.2 link	c.-212C>T		5_prime_UTR_variant	Exon 2 of 15		NP_001305298.1	Q9Y345-2Q4VAM4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6 link	c.352C>T	p.Leu118Leu	synonymous_variant	Exon 2 of 16	1	NM_004211.5	ENSP00000434364.2		Q9Y345-1
SLC6A5	ENST00000298923.11 link	n.352C>T		non_coding_transcript_exon_variant	Exon 2 of 15	1		ENSP00000298923.7		J3KNC4

Frequencies

GnomAD3 genomes

AF:

0.324

AC:

49306

AN:

152020

Hom.:

8101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.308

Gnomad AMI

AF:

0.353

Gnomad AMR

AF:

0.313

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.358

Gnomad SAS

AF:

0.276

Gnomad FIN

AF:

0.373

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.330

Gnomad OTH

AF:

0.324

GnomAD2 exomes

AF:

0.331

AC:

80808

AN:

243960

AF XY:

0.328

show subpopulations

Gnomad AFR exome

AF:

0.309

Gnomad AMR exome

AF:

0.337

Gnomad ASJ exome

AF:

0.328

Gnomad EAS exome

AF:

0.354

Gnomad FIN exome

AF:

0.378

Gnomad NFE exome

AF:

0.337

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.334

AC:

487354

AN:

1459676

Hom.:

81991

Cov.:

AF XY:

0.331

AC XY:

240399

AN XY:

726028

show subpopulations

African (AFR)

AF:

0.301

AC:

10054

AN:

33448

American (AMR)

AF:

0.335

AC:

14857

AN:

44348

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

8568

AN:

26078

East Asian (EAS)

AF:

0.394

AC:

15598

AN:

39624

South Asian (SAS)

AF:

0.274

AC:

23529

AN:

85996

European-Finnish (FIN)

AF:

0.380

AC:

20194

AN:

53164

Middle Eastern (MID)

AF:

0.287

AC:

1652

AN:

5764

European-Non Finnish (NFE)

AF:

0.336

AC:

373824

AN:

1111004

Other (OTH)

AF:

0.317

AC:

19078

AN:

60250

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

20520

41041

61561

82082

102602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12154

24308

36462

48616

60770

<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:

0.324

AC:

49358

AN:

152138

Hom.:

8118

Cov.:

AF XY:

0.325

AC XY:

24153

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.308

AC:

12776

AN:

41516

American (AMR)

AF:

0.313

AC:

4792

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1152

AN:

3472

East Asian (EAS)

AF:

0.358

AC:

1845

AN:

5150

South Asian (SAS)

AF:

0.276

AC:

1334

AN:

4828

European-Finnish (FIN)

AF:

0.373

AC:

3943

AN:

10584

Middle Eastern (MID)

AF:

0.272

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.330

AC:

22439

AN:

67982

Other (OTH)

AF:

0.320

AC:

676

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1762

3523

5285

7046

8808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

492

984

1476

1968

2460

<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:

0.326

Hom.:

23454

Bravo

AF:

0.326

Asia WGS

AF:

0.286

AC:

994

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hyperekplexia 3

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hyperekplexia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.2

(source)

DANN

Benign

0.89

PhyloP100

0.75

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over