Variant 12-191211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001122848.3(SLC6A12):c.1702C>T(p.Arg568Cys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000108 in 1,114,384 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLC6A12
NM_001122848.3 missense, splice_region

Scores

Splicing: ADA: 0.9878

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.26

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.882

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A12	NM_001122848.3 linkuse as main transcript	c.1702C>T	p.Arg568Cys	missense_variant, splice_region_variant	16/16	ENST00000684302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A12	ENST00000684302.1 linkuse as main transcript	c.1702C>T	p.Arg568Cys	missense_variant, splice_region_variant	16/16		NM_001122848.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000108

AC:

AN:

1114384

Hom.:

Cov.:

AF XY:

0.0000114

AC XY:

AN XY:

528272

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000369

Gnomad4 SAS exome

AF:

0.0000846

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000862

Gnomad4 OTH exome

AF:

0.0000223

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000103

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 18, 2024

The c.1702C>T (p.R568C) alteration is located in exon 17 (coding exon 14) of the SLC6A12 gene. This alteration results from a C to T substitution at nucleotide position 1702, causing the arginine (R) at amino acid position 568 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.17

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.38

T;T;T;T

Eigen

Benign

0.16

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;.;.;.

M_CAP

Uncertain

0.16

MetaRNN

Pathogenic

0.88

D;D;D;D

MetaSVM

Benign

-0.37

MutationAssessor

Benign

0.97

L;L;L;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-6.2

D;D;D;D

REVEL

Uncertain

0.58

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

0.83

P;P;P;P

Vest4

0.53

MutPred

0.78

Gain of catalytic residue at L569 (P = 0.0194);Gain of catalytic residue at L569 (P = 0.0194);Gain of catalytic residue at L569 (P = 0.0194);Gain of catalytic residue at L569 (P = 0.0194);

MVP

0.88

ClinPred

0.96

GERP RS

5.1

Varity_R

0.62

gMVP

0.63

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.87

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