Variant chr3-10874978-G-A 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_014229.3(SLC6A11):c.774G>A(p.Ala258Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00577 in 1,612,228 control chromosomes in the GnomAD database, including 447 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 231 hom., cov: 33)

Exomes 𝑓: 0.0032 ( 216 hom. )

Consequence

SLC6A11
NM_014229.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -4.44

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 made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 3-10874978-G-A is Benign according to our data. Variant chr3-10874978-G-A is described in ClinVar as [Benign]. Clinvar id is 788968.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.44 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A11	NM_014229.3 link	c.774G>A	p.Ala258Ala	synonymous_variant	6/14	ENST00000254488.7	NP_055044.1	P48066-1
SLC6A11	XM_047448764.1 link	c.252G>A	p.Ala84Ala	synonymous_variant	4/12		XP_047304720.1
SLC6A11	XM_011534033.3 link	c.774G>A	p.Ala258Ala	synonymous_variant	6/9		XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7 link	c.774G>A	p.Ala258Ala	synonymous_variant	6/14	1	NM_014229.3	ENSP00000254488.2		P48066-1

Frequencies

GnomAD3 genomes

AF:

0.0301

AC:

4575

AN:

152096

Hom.:

228

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.0186

GnomAD3 exomes

AF:

0.00798

AC:

1995

AN:

250018

Hom.:

AF XY:

0.00566

AC XY:

765

AN XY:

135118

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00527

Gnomad ASJ exome

AF:

0.000299

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000353

Gnomad OTH exome

AF:

0.00394

GnomAD4 exome

AF:

0.00323

AC:

4711

AN:

1460014

Hom.:

216

Cov.:

AF XY:

0.00276

AC XY:

2008

AN XY:

726318

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.00559

Gnomad4 ASJ exome

AF:

0.0000767

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.000279

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.00771

GnomAD4 genome

AF:

0.0302

AC:

4597

AN:

152214

Hom.:

231

Cov.:

AF XY:

0.0294

AC XY:

2191

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000338

Gnomad4 OTH

AF:

0.0184

Alfa

AF:

0.0160

Hom.:

Bravo

AF:

0.0356

Asia WGS

AF:

0.00751

AC:

AN:

3478

EpiCase

AF:

0.000165

EpiControl

AF:

0.000418

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 21, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.19

DANN

Benign

0.47

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