Genetic Variant SLC6A1:p.Ala2Val (chr3-11017216-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP6_Moderate

The NM_003042.4(SLC6A1):c.5C>T(p.Ala2Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,250 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A2E) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC6A1
NM_003042.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.52

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP6

Variant 3-11017216-C-T is Benign according to our data. Variant chr3-11017216-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2155429.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4 link	c.5C>T	p.Ala2Val	missense_variant	Exon 3 of 16	ENST00000287766.10	NP_003033.3	A0A024R2K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10 link	c.5C>T	p.Ala2Val	missense_variant	Exon 3 of 16	1	NM_003042.4	ENSP00000287766.4		P30531

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461250

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726844

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26128

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86226

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53264

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5716

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111650

Other (OTH)

AF:

0.00

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Epilepsy with myoclonic atonic seizures

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.37

BayesDel_addAF

Uncertain

0.070

BayesDel_noAF

Benign

-0.14

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.27

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

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.25

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

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.47

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

Benign

-0.42

MutationAssessor

Benign

0.97

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

PhyloP100

5.5

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.70

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

REVEL

Uncertain

0.29

Sift

Uncertain

0.0090

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

Sift4G

Uncertain

0.013

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

Polyphen

0.99

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

Vest4

0.63

MutPred

0.20

Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);Gain of MoRF binding (P = 0.0994);

MVP

0.67

MPC

1.8

ClinPred

0.92

GERP RS

4.4

PromoterAI

-0.095

Neutral

(source)

Varity_R

0.10

gMVP

0.66

Mutation Taster

=73/27

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over