12-191132-C-G

Variant names:

• chr12-191132-C-G
• rs537332809
• NM_001122848.3:c.1781G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001122848.3(SLC6A12):​c.1781G>C​(p.Arg594Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000836 in 1,195,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. 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. R594Q) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.531
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057125926).

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.1781G>C	p.Arg594Pro	missense	Exon 16 of 16	NP_001116320.1	P48065
	SLC6A12	NM_001122847.3		c.1781G>C	p.Arg594Pro	missense	Exon 16 of 16	NP_001116319.1	P48065
	SLC6A12	NM_001206931.2		c.1781G>C	p.Arg594Pro	missense	Exon 15 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.1781G>C	p.Arg594Pro	missense	Exon 16 of 16	ENSP00000508194.1	P48065
	SLC6A12	ENST00000359674.8	TSL:1	c.1781G>C	p.Arg594Pro	missense	Exon 16 of 16	ENSP00000352702.4	P48065
	SLC6A12	ENST00000397296.6	TSL:1	c.1781G>C	p.Arg594Pro	missense	Exon 15 of 15	ENSP00000380464.2	P48065

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.36e-7 AC: 1 AN: 1195706 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 577956

African (AFR) AF: 0.00 AC: 0 AN: 25846

American (AMR) AF: 0.00 AC: 0 AN: 22230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17486

East Asian (EAS) AF: 0.0000326 AC: 1 AN: 30638

South Asian (SAS) AF: 0.00 AC: 0 AN: 35670

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4872

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 968534

Other (OTH) AF: 0.00 AC: 0 AN: 47998

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.76
DANN	Benign	0.36
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.33	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.53
PrimateAI	Benign	0.20	T
PROVEAN	Benign	0.54	N
REVEL	Benign	0.070
Sift	Benign	0.29	T
Sift4G	Benign	0.30	T
Polyphen		0.0	B
Vest4		0.090
MutPred		0.22		Gain of glycosylation at S591 (P = 0.0478)
MVP		0.29
ClinPred		0.083	T
GERP RS		-4.4
Varity_R		0.096
gMVP		0.39
Mutation Taster		=93/7	polymorphism

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: rs537332809; hg19: chr12-300298;