Genetic Variant NM_014229.3:c.71C>T (chr3-10816336-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014229.3(SLC6A11):c.71C>T(p.Pro24Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC6A11
NM_014229.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.00

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.086889505).

BP6

Variant 3-10816336-C-T is Benign according to our data. Variant chr3-10816336-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2534596.Status of the report is criteria_provided_single_submitter, 1 stars.

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.71C>T	p.Pro24Leu	missense	Exon 1 of 14	NP_055044.1	P48066-1
	SLC6A11	NM_001317406.3		c.71C>T	p.Pro24Leu	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.71C>T	p.Pro24Leu	missense	Exon 1 of 14	ENSP00000254488.2	P48066-1
SLC6A11	ENST00000454147.1	TSL:1	c.71C>T	p.Pro24Leu	missense	Exon 1 of 4	ENSP00000404120.1	P48066-2
SLC6A11	ENST00000861594.1		c.71C>T	p.Pro24Leu	missense	Exon 1 of 12	ENSP00000531653.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1264952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

621202

African (AFR)

AF:

0.00

AC:

AN:

24260

American (AMR)

AF:

0.00

AC:

AN:

13892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18802

East Asian (EAS)

AF:

0.00

AC:

AN:

27840

South Asian (SAS)

AF:

0.00

AC:

AN:

58514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1021076

Other (OTH)

AF:

0.00

AC:

AN:

51436

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.088

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.086

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.63

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PhyloP100

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.41

REVEL

Benign

0.085

Sift

Benign

0.29

Sift4G

Benign

0.21

Polyphen

0.0

Vest4

0.072

MutPred

0.20

Loss of loop (P = 0.0153)

MVP

0.43

MPC

0.62

ClinPred

0.14

GERP RS

-0.99

PromoterAI

-0.031

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.027

gMVP

0.14

Mutation Taster

=91/9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over