Variant 11-20599640-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004211.5(SLC6A5):c.-33C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 1,613,326 control chromosomes in the GnomAD database, including 8,349 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 645 hom., cov: 32)

Exomes 𝑓: 0.099 ( 7704 hom. )

Consequence

SLC6A5
NM_004211.5 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.772

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 11-20599640-C-T is Benign according to our data. Variant chr11-20599640-C-T is described in ClinVar as [Benign]. Clinvar id is 303991.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A5	NM_004211.5 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant	1/16	ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2 linkuse as main transcript	c.-596C>T		5_prime_UTR_variant	1/15		NP_001305298.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant	1/16	1	NM_004211.5	ENSP00000434364	P1	Q9Y345-1
SLC6A5	ENST00000298923.11 linkuse as main transcript	c.-33C>T		5_prime_UTR_variant, NMD_transcript_variant	1/15	1		ENSP00000298923

Frequencies

GnomAD3 genomes

AF:

0.0860

AC:

13079

AN:

152140

Hom.:

644

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0606

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0603

Gnomad ASJ

AF:

0.0954

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0944

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.0979

GnomAD3 exomes

AF:

0.0870

AC:

21878

AN:

251464

Hom.:

1138

AF XY:

0.0919

AC XY:

12490

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.0586

Gnomad AMR exome

AF:

0.0418

Gnomad ASJ exome

AF:

0.0977

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.104

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.106

Gnomad OTH exome

AF:

0.0902

GnomAD4 exome

AF:

0.0990

AC:

144648

AN:

1461068

Hom.:

7704

Cov.:

AF XY:

0.0996

AC XY:

72382

AN XY:

726884

show subpopulations

Gnomad4 AFR exome

AF:

0.0621

Gnomad4 AMR exome

AF:

0.0430

Gnomad4 ASJ exome

AF:

0.0974

Gnomad4 EAS exome

AF:

0.000353

Gnomad4 SAS exome

AF:

0.103

Gnomad4 FIN exome

AF:

0.118

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.0937

GnomAD4 genome

AF:

0.0859

AC:

13076

AN:

152258

Hom.:

645

Cov.:

AF XY:

0.0872

AC XY:

6488

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0605

Gnomad4 AMR

AF:

0.0602

Gnomad4 ASJ

AF:

0.0954

Gnomad4 EAS

AF:

0.00135

Gnomad4 SAS

AF:

0.0941

Gnomad4 FIN

AF:

0.126

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.0959

Alfa

AF:

0.0953

Hom.:

186

Bravo

AF:

0.0797

Asia WGS

AF:

0.0470

AC:

163

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

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

-0.66

CADD

Benign

DANN

Benign

0.84

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

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