Genetic Variant SLC6A12:p.Val430Ile (chr12-196162-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001122848.3(SLC6A12):c.1288G>A(p.Val430Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000204 in 1,571,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

SLC6A12
NM_001122848.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0330

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04203403).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A12	NM_001122848.3 link	c.1288G>A	p.Val430Ile	missense_variant	Exon 12 of 16	ENST00000684302.1	NP_001116320.1	P48065

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A12	ENST00000684302.1 link	c.1288G>A	p.Val430Ile	missense_variant	Exon 12 of 16		NM_001122848.3	ENSP00000508194.1		P48065

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000708

AC:

AN:

183528

Hom.:

AF XY:

0.0000411

AC XY:

AN XY:

97226

show subpopulations

Gnomad AFR exome

AF:

0.000176

Gnomad AMR exome

AF:

0.0000386

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000211

Gnomad SAS exome

AF:

0.0000817

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000646

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000190

AC:

AN:

1419610

Hom.:

Cov.:

AF XY:

0.0000228

AC XY:

AN XY:

701456

show subpopulations

Gnomad4 AFR exome

AF:

0.0000603

Gnomad4 AMR exome

AF:

0.0000272

Gnomad4 ASJ exome

AF:

0.0000395

Gnomad4 EAS exome

AF:

0.0000780

Gnomad4 SAS exome

AF:

0.0000866

Gnomad4 FIN exome

AF:

0.0000198

Gnomad4 NFE exome

AF:

0.0000101

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000117

AC:

ExAC

AF:

0.0000422

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.52

CADD

Benign

1.0

DANN

Benign

0.82

DEOGEN2

Benign

0.024

T;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.59

T;.;.;.

M_CAP

Benign

0.035

MetaRNN

Benign

0.042

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.92

L;L;L;L

PrimateAI

Benign

0.25

PROVEAN

Benign

0.060

N;N;N;N

REVEL

Benign

0.051

Sift

Benign

0.88

T;T;T;T

Sift4G

Benign

0.62

T;T;T;T

Polyphen

0.017

B;B;B;B

Vest4

0.13

MVP

0.34

ClinPred

0.0053

GERP RS

-0.88

Varity_R

0.021

gMVP

0.097

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