12-196772-G-C

Position:

• chr12-196772-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001122848.3(SLC6A12):​c.1186C>G​(p.Gln396Glu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC6A12 NM_001122848.3 missense, splice_region
• Scores: Splicing: ADA: 0.1869
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.95

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

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.79

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A12	NM_001122848.3	c.1186C>G	p.Gln396Glu	missense_variant, splice_region_variant	11/16	ENST00000684302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A12	ENST00000684302.1	c.1186C>G	p.Gln396Glu	missense_variant, splice_region_variant	11/16		NM_001122848.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 23, 2023

The c.1186C>G (p.Q396E) alteration is located in exon 12 (coding exon 9) of the SLC6A12 gene. This alteration results from a C to G substitution at nucleotide position 1186, causing the glutamine (Q) at amino acid position 396 to be replaced by a glutamic acid (E). 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	Benign	0.16
BayesDel_addAF	Benign	0.0083	T
BayesDel_noAF	Benign	-0.23
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T;T;T;T
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.45
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.94	D;.;.;.
M_CAP	Benign	0.055	D
MetaRNN	Pathogenic	0.79	D;D;D;D
MetaSVM	Uncertain	-0.033	T
MutationAssessor	Benign	1.4	L;L;L;L
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Uncertain	0.51
Sift	Benign	0.073	T;T;T;T
Sift4G	Benign	0.075	T;T;T;T
Polyphen		0.85	P;P;P;P
Vest4		0.59
MutPred		0.72		Loss of stability (P = 0.1513);Loss of stability (P = 0.1513);Loss of stability (P = 0.1513);Loss of stability (P = 0.1513);
MVP		0.86
ClinPred		0.97	D
GERP RS		3.3
Varity_R		0.33
gMVP		0.73

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.19
dbscSNV1_RF	Benign	0.42
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-305938;