Variant chr3-11017216-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2

The NM_003042.4(SLC6A1):c.5C>A(p.Ala2Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000123 in 1,461,252 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2V) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

SLC6A1
NM_003042.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 5.52

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:

SLC6A1-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

SLC6A1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant where missense usually causes diseases, SLC6A1

BP6

Variant 3-11017216-C-A is Benign according to our data. Variant chr3-11017216-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 1188750.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAdExome4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	3/16	ENST00000287766.10
SLC6A1-AS1	NR_046647.1 linkuse as main transcript	n.105+1904G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10 linkuse as main transcript	c.5C>A	p.Ala2Glu	missense_variant	3/16	1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2 linkuse as main transcript	n.105+1904G>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1461252

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726846

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000564

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Sep 10, 2021

Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect -

Myoclonic-atonic epilepsy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 26, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.16

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;.;T;.;T;T;.;.;.

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.93

M_CAP

Benign

0.049

MetaRNN

Uncertain

0.44

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.28

MutationAssessor

Benign

0.97

L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;L;.;L;.;L;L;.;.;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.73

Polyphen

0.99

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;.;D;.;D;D;.;.;.

Vest4

0.44

MutPred

0.24

Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);Loss of MoRF binding (P = 0.0308);

MVP

0.54

MPC

2.2

ClinPred

0.91

GERP RS

4.4

Varity_R

0.19

gMVP

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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