Variant 3-11022405-G-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_003042.4(SLC6A1):c.651G>T(p.Thr217Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0479 in 1,613,392 control chromosomes in the GnomAD database, including 2,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. T217T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.041 ( 172 hom., cov: 33)

Exomes 𝑓: 0.049 ( 2126 hom. )

Consequence

SLC6A1
NM_003042.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.33

Variant links:

Genes affected

SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]

SLC6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 3-11022405-G-T is Benign according to our data. Variant chr3-11022405-G-T is described in ClinVar as [Benign]. Clinvar id is 448418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.651G>T	p.Thr217Thr	synonymous_variant	7/16	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.651G>T	p.Thr217Thr	synonymous_variant	7/16	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

AF:

0.0413

AC:

6279

AN:

152206

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0304

Gnomad AMI

AF:

0.0504

Gnomad AMR

AF:

0.0308

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.0485

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.0312

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0438

Gnomad OTH

AF:

0.0425

GnomAD3 exomes

AF:

0.0509

AC:

12717

AN:

249628

Hom.:

485

AF XY:

0.0558

AC XY:

7527

AN XY:

134884

show subpopulations

Gnomad AFR exome

AF:

0.0308

Gnomad AMR exome

AF:

0.0170

Gnomad ASJ exome

AF:

0.0659

Gnomad EAS exome

AF:

0.0434

Gnomad SAS exome

AF:

0.127

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.0462

Gnomad OTH exome

AF:

0.0500

GnomAD4 exome

AF:

0.0485

AC:

70931

AN:

1461068

Hom.:

2126

Cov.:

AF XY:

0.0512

AC XY:

37225

AN XY:

726752

show subpopulations

Gnomad4 AFR exome

AF:

0.0325

Gnomad4 AMR exome

AF:

0.0189

Gnomad4 ASJ exome

AF:

0.0646

Gnomad4 EAS exome

AF:

0.0457

Gnomad4 SAS exome

AF:

0.126

Gnomad4 FIN exome

AF:

0.0383

Gnomad4 NFE exome

AF:

0.0442

Gnomad4 OTH exome

AF:

0.0510

GnomAD4 genome

AF:

0.0412

AC:

6278

AN:

152324

Hom.:

172

Cov.:

AF XY:

0.0418

AC XY:

3116

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0304

Gnomad4 AMR

AF:

0.0307

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.0479

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.0312

Gnomad4 NFE

AF:

0.0438

Gnomad4 OTH

AF:

0.0421

Alfa

AF:

0.0440

Hom.:

176

Bravo

AF:

0.0397

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jun 21, 2017	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -

Epilepsy with myoclonic atonic seizures

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 04, 2025

- -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 15, 2016

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

6.2

DANN

Benign

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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