Variant 12-193326-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001122848.3(SLC6A12):c.1481G>C(p.Trp494Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,084 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0017 ( 11 hom. )

Consequence

SLC6A12
NM_001122848.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.47

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:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011738628).

BP6

Variant 12-193326-C-G is Benign according to our data. Variant chr12-193326-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2642560.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A12	NM_001122848.3 linkuse as main transcript	c.1481G>C	p.Trp494Ser	missense_variant	14/16	ENST00000684302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A12	ENST00000684302.1 linkuse as main transcript	c.1481G>C	p.Trp494Ser	missense_variant	14/16		NM_001122848.3	P1
	ENST00000544067.1 linkuse as main transcript	n.145+146C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00204

AC:

310

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00265

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00195

AC:

491

AN:

251390

Hom.:

AF XY:

0.00186

AC XY:

253

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.000794

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0100

Gnomad NFE exome

AF:

0.00205

Gnomad OTH exome

AF:

0.00196

GnomAD4 exome

AF:

0.00166

AC:

2422

AN:

1461772

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1211

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000447

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00824

Gnomad4 NFE exome

AF:

0.00168

Gnomad4 OTH exome

AF:

0.00128

GnomAD4 genome

AF:

0.00204

AC:

310

AN:

152312

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00265

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00297

Hom.:

Bravo

AF:

0.000975

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00221

AC:

ExAC

AF:

0.00191

AC:

232

EpiCase

AF:

0.00147

EpiControl

AF:

0.00148

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jan 01, 2023

SLC6A12: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.13

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.21

T;T;T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.020

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.79

T;.;.;.

MetaRNN

Benign

0.012

T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.17

N;N;N;N

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.55

PROVEAN

Uncertain

-3.9

D;D;D;D

REVEL

Uncertain

0.40

Sift

Benign

0.50

T;T;T;T

Sift4G

Benign

0.47

T;T;T;T

Polyphen

0.024

B;B;B;B

Vest4

0.44

MVP

0.69

ClinPred

0.033

GERP RS

4.8

Varity_R

0.56

gMVP

0.74

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over