Genetic Variant NM_014229.3:c.110G>T (chr3-10816375-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014229.3(SLC6A11):c.110G>T(p.Arg37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,485,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R37H) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

SLC6A11
NM_014229.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19

Publications

0 publications found

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]

SLC6A11 links:

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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;

BP4

Computational evidence support a benign effect (MetaRNN=0.22061235).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014229.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A11	NM_014229.3	MANE Select	c.110G>T	p.Arg37Leu	missense	Exon 1 of 14	NP_055044.1	P48066-1
	SLC6A11	NM_001317406.3		c.110G>T	p.Arg37Leu	missense	Exon 1 of 4	NP_001304335.1	P48066-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC6A11	ENST00000254488.7	TSL:1 MANE Select	c.110G>T	p.Arg37Leu	missense	Exon 1 of 14	ENSP00000254488.2	P48066-1
SLC6A11	ENST00000454147.1	TSL:1	c.110G>T	p.Arg37Leu	missense	Exon 1 of 4	ENSP00000404120.1	P48066-2
SLC6A11	ENST00000861594.1		c.110G>T	p.Arg37Leu	missense	Exon 1 of 12	ENSP00000531653.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000589

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000169

AC:

AN:

118158

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000269

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000352

AC:

AN:

1334026

Hom.:

Cov.:

AF XY:

0.0000288

AC XY:

AN XY:

658694

show subpopulations

African (AFR)

AF:

0.0000374

AC:

AN:

26730

American (AMR)

AF:

0.00

AC:

AN:

25732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22618

East Asian (EAS)

AF:

0.00

AC:

AN:

29728

South Asian (SAS)

AF:

0.00

AC:

AN:

70370

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48706

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4374

European-Non Finnish (NFE)

AF:

0.0000438

AC:

AN:

1051156

Other (OTH)

AF:

0.00

AC:

AN:

54612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74202

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000589

AC:

AN:

67942

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000284

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000257

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.092

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.56

M_CAP

Pathogenic

0.86

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.77

MutationAssessor

Benign

0.0

PhyloP100

3.2

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.22

REVEL

Benign

0.14

Sift

Benign

0.37

Sift4G

Benign

0.29

Polyphen

0.013

Vest4

0.24

MutPred

0.43

Loss of solvent accessibility (P = 0.0155)

MVP

0.60

MPC

0.76

ClinPred

0.053

GERP RS

2.2

PromoterAI

-0.026

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.12

gMVP

0.23

Mutation Taster

=86/14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over