chr12-193326-C-A

Variant names:

• chr12-193326-C-A
• rs138178078
• NM_001122848.3:c.1481G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001122848.3(SLC6A12):​c.1481G>T​(p.Trp494Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 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: not found (cov: 33)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47

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]

ENSG00000255671 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A12	NM_001122848.3	c.1481G>T	p.Trp494Leu	missense_variant	Exon 14 of 16	ENST00000684302.1	NP_001116320.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A12	ENST00000684302.1	c.1481G>T	p.Trp494Leu	missense_variant	Exon 14 of 16		NM_001122848.3	ENSP00000508194.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000330 AC: 4

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Benign	0.93
DEOGEN2	Benign	0.20	T;T;T;T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.072
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.86	D;.;.;.
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.44	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.70	N;N;N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D;D;D;D
REVEL	Uncertain	0.31
Sift	Benign	0.88	T;T;T;T
Sift4G	Benign	0.71	T;T;T;T
Polyphen		0.0060	B;B;B;B
Vest4		0.61
MutPred		0.65		Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);Gain of relative solvent accessibility (P = 0.1259);
MVP		0.69
ClinPred		0.98	D
GERP RS		4.8
Varity_R		0.35
gMVP		0.71

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

Other links and lift over

dbSNP: rs138178078; hg19: chr12-302492;