Variant rs759515813 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP6_Moderate

The NM_003042.4(SLC6A1):c.1213A>C(p.Ile405Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC6A1
NM_003042.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.17

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 (HGNC:):

SLC6A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SLC6A1. . Gene score misZ 4.1766 (greater than the threshold 3.09). Trascript score misZ 4.9229 (greater than threshold 3.09). GenCC has associacion of gene with myoclonic-atonic epilepsy, myoclonic-astatic epilepsy.

BP6

Variant 3-11029242-A-C is Benign according to our data. Variant chr3-11029242-A-C is described in ClinVar as [Benign]. Clinvar id is 1167091.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A1	NM_003042.4 linkuse as main transcript	c.1213A>C	p.Ile405Leu	missense_variant	12/16	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 linkuse as main transcript	c.1213A>C	p.Ile405Leu	missense_variant	12/16	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Myoclonic-atonic epilepsy

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Oct 05, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.25

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

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

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

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.67

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Benign

1.8

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

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-1.7

.;N;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.51

Sift

Uncertain

0.020

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

Sift4G

Uncertain

0.049

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

Polyphen

0.031

B;B;B;B;B;.;B;.;B;B;B;B;.;B;B;B;.;B;B;B;.;B;B;B;.

Vest4

0.58

MutPred

0.62

Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);Loss of catalytic residue at I405 (P = 0.1211);.;

MVP

0.74

MPC

1.2

ClinPred

0.90

GERP RS

5.6

Varity_R

0.55

gMVP

0.89

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over