chr3-10823379-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014229.3(SLC6A11):ā€‹c.610A>Gā€‹(p.Met204Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 33)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

SLC6A11
NM_014229.3 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.38
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1278565).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC6A11NM_014229.3 linkuse as main transcriptc.610A>G p.Met204Val missense_variant 4/14 ENST00000254488.7 NP_055044.1
SLC6A11NM_001317406.3 linkuse as main transcriptc.610A>G p.Met204Val missense_variant 4/4 NP_001304335.1
SLC6A11XM_011534033.3 linkuse as main transcriptc.610A>G p.Met204Val missense_variant 4/9 XP_011532335.1
SLC6A11XM_047448764.1 linkuse as main transcriptc.33A>G p.Ser11= synonymous_variant 1/12 XP_047304720.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC6A11ENST00000254488.7 linkuse as main transcriptc.610A>G p.Met204Val missense_variant 4/141 NM_014229.3 ENSP00000254488 P1P48066-1
SLC6A11ENST00000454147.1 linkuse as main transcriptc.610A>G p.Met204Val missense_variant 4/41 ENSP00000404120 P48066-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251472
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135912
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460228
Hom.:
0
Cov.:
29
AF XY:
0.00000138
AC XY:
1
AN XY:
726538
show subpopulations
Gnomad4 AFR exome
AF:
0.00
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:
9.00e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152180
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74348
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 01, 2024The c.610A>G (p.M204V) alteration is located in exon 4 (coding exon 4) of the SLC6A11 gene. This alteration results from a A to G substitution at nucleotide position 610, causing the methionine (M) at amino acid position 204 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.076
BayesDel_addAF
Benign
-0.086
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
21
DANN
Benign
0.92
DEOGEN2
Benign
0.038
T;.
Eigen
Benign
-0.054
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.84
T;T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-0.89
T
MutationAssessor
Benign
-0.51
N;N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
0.55
N;N
REVEL
Benign
0.17
Sift
Benign
0.81
T;T
Sift4G
Benign
0.64
T;T
Polyphen
0.0
B;.
Vest4
0.28
MutPred
0.38
Gain of glycosylation at S201 (P = 0.155);Gain of glycosylation at S201 (P = 0.155);
MVP
0.72
MPC
0.65
ClinPred
0.25
T
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.18
gMVP
0.56

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.

Other links and lift over

dbSNP: rs754830826; hg19: chr3-10865064; API