Variant 11-20601477-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004211.5(SLC6A5):c.352C>T(p.Leu118=) 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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 ClinVar 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 Lovd as [Benign].

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/exons	MANE	UniProt
SLC6A5	NM_004211.5 linkuse as main transcript	c.352C>T	p.Leu118=	synonymous_variant	2/16	ENST00000525748.6
SLC6A5	NM_001318369.2 linkuse as main transcript	c.-212C>T		5_prime_UTR_variant	2/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A5	ENST00000525748.6 linkuse as main transcript	c.352C>T	p.Leu118=	synonymous_variant	2/16	1	NM_004211.5	P1	Q9Y345-1
SLC6A5	ENST00000298923.11 linkuse as main transcript	c.352C>T	p.Leu118=	synonymous_variant, NMD_transcript_variant	2/15	1

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

GnomAD3 exomes

AF:

0.331

AC:

80808

AN:

243960

Hom.:

13280

AF XY:

0.328

AC XY:

43418

AN XY:

132548

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 SAS exome

AF:

0.276

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

Gnomad4 AFR exome

AF:

0.301

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.329

Gnomad4 EAS exome

AF:

0.394

Gnomad4 SAS exome

AF:

0.274

Gnomad4 FIN exome

AF:

0.380

Gnomad4 NFE exome

AF:

0.336

Gnomad4 OTH exome

AF:

0.317

GnomAD4 genome

AF:

0.324

AC:

49358

AN:

152138

Hom.:

8118

Cov.:

AF XY:

0.325

AC XY:

24153

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.308

Gnomad4 AMR

AF:

0.313

Gnomad4 ASJ

AF:

0.332

Gnomad4 EAS

AF:

0.358

Gnomad4 SAS

AF:

0.276

Gnomad4 FIN

AF:

0.373

Gnomad4 NFE

AF:

0.330

Gnomad4 OTH

AF:

0.320

Alfa

AF:

0.324

Hom.:

15040

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

Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Hyperekplexia 3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hyperekplexia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

9.2

DANN

Benign

0.89

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over