12-193326-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001122848.3(SLC6A12):​c.1481G>C​(p.Trp494Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00169 in 1,614,084 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (4 hom., cov: 33)
  • Exomes 𝑓: 0.0017 (11 hom.)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011738628).
• BP6: Variant 12-193326-C-G is Benign according to our data. Variant chr12-193326-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2642560.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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>C	p.Trp494Ser	missense	Exon 14 of 16	NP_001116320.1	P48065
	SLC6A12	NM_001122847.3		c.1481G>C	p.Trp494Ser	missense	Exon 14 of 16	NP_001116319.1	P48065
	SLC6A12	NM_001206931.2		c.1481G>C	p.Trp494Ser	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>C	p.Trp494Ser	missense	Exon 14 of 16	ENSP00000508194.1	P48065
	SLC6A12	ENST00000359674.8	TSL:1	c.1481G>C	p.Trp494Ser	missense	Exon 14 of 16	ENSP00000352702.4	P48065
	SLC6A12	ENST00000397296.6	TSL:1	c.1481G>C	p.Trp494Ser	missense	Exon 13 of 15	ENSP00000380464.2	P48065

Frequencies

GnomAD3 genomes AF: 0.00204 AC: 310 AN: 152194 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00265

Gnomad OTH AF: 0.000956

GnomAD2 exomes AF: 0.00195 AC: 491 AN: 251390 AF XY: 0.00186

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000794

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0100

Gnomad NFE exome AF: 0.00205

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.00166 AC: 2422 AN: 1461772 Hom.: 11 Cov.: 30 AF XY: 0.00167 AC XY: 1211 AN XY: 727198

African (AFR) AF: 0.000179 AC: 6 AN: 33478

American (AMR) AF: 0.000447 AC: 20 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86250

European-Finnish (FIN) AF: 0.00824 AC: 440 AN: 53390

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00168 AC: 1863 AN: 1111944

Other (OTH) AF: 0.00128 AC: 77 AN: 60392

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152312 Hom.: 4 Cov.: 33 AF XY: 0.00238 AC XY: 177 AN XY: 74474

African (AFR) AF: 0.000241 AC: 10 AN: 41566

American (AMR) AF: 0.000588 AC: 9 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.0101 AC: 107 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00265 AC: 180 AN: 68012

Other (OTH) AF: 0.000946 AC: 2 AN: 2114

Alfa AF: 0.00297 Hom.: 2

Bravo AF: 0.000975

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00191 AC: 232

EpiCase AF: 0.00147

EpiControl AF: 0.00148

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.13
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.79	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-0.80	T
MutationAssessor	Benign	0.17	N
PhyloP100		1.5
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.40
Sift	Benign	0.50	T
Sift4G	Benign	0.47	T
Polyphen		0.024	B
Vest4		0.44
MVP		0.69
ClinPred		0.033	T
GERP RS		4.8
Varity_R		0.56
gMVP		0.74
Mutation Taster		=99/1	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: rs138178078; hg19: chr12-302492; COSMIC: COSV62884086; COSMIC: COSV62884086;