rs138178078

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-193326-C-A
• chr12-193326-C-G
• chr12-193326-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W494S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.47
• Publications: 3 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122848.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A12	NM_001122848.3	MANE Select	c.1481G>T	p.Trp494Leu	missense	Exon 14 of 16	NP_001116320.1	P48065
	SLC6A12	NM_001122847.3		c.1481G>T	p.Trp494Leu	missense	Exon 14 of 16	NP_001116319.1	P48065
	SLC6A12	NM_001206931.2		c.1481G>T	p.Trp494Leu	missense	Exon 13 of 15	NP_001193860.1	P48065

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A12	ENST00000684302.1	MANE Select	c.1481G>T	p.Trp494Leu	missense	Exon 14 of 16	ENSP00000508194.1	P48065
	SLC6A12	ENST00000359674.8	TSL:1	c.1481G>T	p.Trp494Leu	missense	Exon 14 of 16	ENSP00000352702.4	P48065
	SLC6A12	ENST00000397296.6	TSL:1	c.1481G>T	p.Trp494Leu	missense	Exon 13 of 15	ENSP00000380464.2	P48065

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 v4.9

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
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
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	0.70	N
PhyloP100		1.5
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.1	D
REVEL	Uncertain	0.31
Sift	Benign	0.88	T
Sift4G	Benign	0.71	T
Polyphen		0.0060	B
Vest4		0.61
MutPred		0.65		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

Other links and lift over

dbSNP: rs138178078; hg19: chr12-302492;