12-196245-C-T

Variant names:

• chr12-196245-C-T
• rs749096418
• NM_001122848.3:c.1205G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001122848.3(SLC6A12):​c.1205G>A​(p.Cys402Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

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.1205G>A	p.Cys402Tyr	missense	Exon 12 of 16	NP_001116320.1	P48065
	SLC6A12	NM_001122847.3		c.1205G>A	p.Cys402Tyr	missense	Exon 12 of 16	NP_001116319.1	P48065
	SLC6A12	NM_001206931.2		c.1205G>A	p.Cys402Tyr	missense	Exon 11 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.1205G>A	p.Cys402Tyr	missense	Exon 12 of 16	ENSP00000508194.1	P48065
	SLC6A12	ENST00000359674.8	TSL:1	c.1205G>A	p.Cys402Tyr	missense	Exon 12 of 16	ENSP00000352702.4	P48065
	SLC6A12	ENST00000397296.6	TSL:1	c.1205G>A	p.Cys402Tyr	missense	Exon 11 of 15	ENSP00000380464.2	P48065

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000127 AC: 3 AN: 235748 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000171

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000825 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.11
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	D
Eigen	Pathogenic	0.77
Eigen_PC	Pathogenic	0.73
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.18	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Uncertain	0.37	D
MutationAssessor	Benign	1.1	L
PhyloP100		6.2
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	-2.3	N
REVEL	Uncertain	0.53
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.65
MutPred		0.60		Loss of sheet (P = 0.0817)
MVP		0.93
ClinPred		0.92	D
GERP RS		5.5
Varity_R		0.68
gMVP		0.68
Mutation Taster		=80/20	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: rs749096418; hg19: chr12-305411;