Variant 12-209959-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001122848.3(SLC6A12):c.28T>C(p.Cys10Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 1,613,410 control chromosomes in the GnomAD database, including 224,172 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.56 ( 24537 hom., cov: 32)

Exomes 𝑓: 0.52 ( 199635 hom. )

Consequence

SLC6A12
NM_001122848.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.15

Variant links:

Genes affected

SLC6A12 (HGNC:11045): (solute carrier family 6 member 12) Enables monocarboxylic acid transmembrane transporter activity. Involved in monocarboxylic acid transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in neuron projection. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC6A12 links:

SLC6A12 (HGNC:):

SLC6A12 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.607937E-6).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A12	NM_001122848.3 linkuse as main transcript	c.28T>C	p.Cys10Arg	missense_variant	3/16	ENST00000684302.1	NP_001116320.1	P48065

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A12	ENST00000684302.1 linkuse as main transcript	c.28T>C	p.Cys10Arg	missense_variant	3/16		NM_001122848.3	ENSP00000508194.1		P48065

Frequencies

GnomAD3 genomes

AF:

0.561

AC:

85164

AN:

151886

Hom.:

24488

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.470

Gnomad ASJ

AF:

0.618

Gnomad EAS

AF:

0.336

Gnomad SAS

AF:

0.559

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.518

Gnomad OTH

AF:

0.561

GnomAD3 exomes

AF:

0.515

AC:

129294

AN:

251198

Hom.:

34191

AF XY:

0.517

AC XY:

70198

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.699

Gnomad AMR exome

AF:

0.419

Gnomad ASJ exome

AF:

0.619

Gnomad EAS exome

AF:

0.345

Gnomad SAS exome

AF:

0.563

Gnomad FIN exome

AF:

0.513

Gnomad NFE exome

AF:

0.523

Gnomad OTH exome

AF:

0.525

GnomAD4 exome

AF:

0.520

AC:

759700

AN:

1461406

Hom.:

199635

Cov.:

AF XY:

0.521

AC XY:

379003

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.709

Gnomad4 AMR exome

AF:

0.426

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.335

Gnomad4 SAS exome

AF:

0.562

Gnomad4 FIN exome

AF:

0.530

Gnomad4 NFE exome

AF:

0.518

Gnomad4 OTH exome

AF:

0.526

GnomAD4 genome

AF:

0.561

AC:

85266

AN:

152004

Hom.:

24537

Cov.:

AF XY:

0.556

AC XY:

41329

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.701

Gnomad4 AMR

AF:

0.469

Gnomad4 ASJ

AF:

0.618

Gnomad4 EAS

AF:

0.336

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.511

Gnomad4 NFE

AF:

0.518

Gnomad4 OTH

AF:

0.561

Alfa

AF:

0.528

Hom.:

31723

Bravo

AF:

0.564

TwinsUK

AF:

0.520

AC:

1927

ALSPAC

AF:

0.525

AC:

2025

ESP6500AA

AF:

0.702

AC:

3094

ESP6500EA

AF:

0.529

AC:

4550

ExAC

AF:

0.524

AC:

63567

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

EpiCase

AF:

0.531

EpiControl

AF:

0.526

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.51

DEOGEN2

Benign

0.017

T;T;T;T;T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.10

T;.;.;.;T;T

MetaRNN

Benign

0.0000036

T;T;T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

N;N;N;N;.;.

PrimateAI

Benign

0.27

PROVEAN

Benign

0.51

N;N;N;N;N;N

REVEL

Benign

0.057

Sift

Benign

0.52

T;T;T;T;T;T

Sift4G

Benign

0.54

T;T;T;T;T;T

Polyphen

0.0

B;B;B;B;.;.

Vest4

0.014

ClinPred

0.0018

GERP RS

2.8

Varity_R

0.052

gMVP

0.18

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over