chr12-202783-A-G

Variant names:

• chr12-202783-A-G
• rs216250
• NM_001122848.3:c.447T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001122848.3(SLC6A12):​c.447T>C​(p.Thr149Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,613,036 control chromosomes in the GnomAD database, including 185,016 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.54 (23402 hom., cov: 33)
  • Exomes 𝑓: 0.47 (161614 hom.)
• Consequence: SLC6A12 NM_001122848.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.156
• Publications: 24 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.156 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

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.447T>C	p.Thr149Thr	synonymous	Exon 5 of 16	NP_001116320.1
	SLC6A12	NM_001122847.3		c.447T>C	p.Thr149Thr	synonymous	Exon 5 of 16	NP_001116319.1
	SLC6A12	NM_001206931.2		c.447T>C	p.Thr149Thr	synonymous	Exon 4 of 15	NP_001193860.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A12	ENST00000684302.1	MANE Select	c.447T>C	p.Thr149Thr	synonymous	Exon 5 of 16	ENSP00000508194.1
	SLC6A12	ENST00000359674.8	TSL:1	c.447T>C	p.Thr149Thr	synonymous	Exon 5 of 16	ENSP00000352702.4
	SLC6A12	ENST00000397296.6	TSL:1	c.447T>C	p.Thr149Thr	synonymous	Exon 4 of 15	ENSP00000380464.2

Frequencies

GnomAD3 genomes AF: 0.542 AC: 82456 AN: 152016 Hom.: 23375 Cov.: 33

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.565

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.544

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.536

GnomAD2 exomes AF: 0.506 AC: 127213 AN: 251272 AF XY: 0.501

Gnomad AFR exome AF: 0.723

Gnomad AMR exome AF: 0.583

Gnomad ASJ exome AF: 0.378

Gnomad EAS exome AF: 0.644

Gnomad FIN exome AF: 0.442

Gnomad NFE exome AF: 0.447

Gnomad OTH exome AF: 0.473

GnomAD4 exome AF: 0.466 AC: 680099 AN: 1460902 Hom.: 161614 Cov.: 38 AF XY: 0.466 AC XY: 338611 AN XY: 726794

African (AFR) AF: 0.730 AC: 24436 AN: 33462

American (AMR) AF: 0.583 AC: 26057 AN: 44704

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 9894 AN: 26122

East Asian (EAS) AF: 0.613 AC: 24309 AN: 39674

South Asian (SAS) AF: 0.535 AC: 46117 AN: 86178

European-Finnish (FIN) AF: 0.434 AC: 23151 AN: 53402

Middle Eastern (MID) AF: 0.524 AC: 3004 AN: 5730

European-Non Finnish (NFE) AF: 0.444 AC: 493549 AN: 1111272

Other (OTH) AF: 0.490 AC: 29582 AN: 60358

GnomAD4 genome AF: 0.543 AC: 82537 AN: 152134 Hom.: 23402 Cov.: 33 AF XY: 0.545 AC XY: 40533 AN XY: 74352

African (AFR) AF: 0.718 AC: 29804 AN: 41500

American (AMR) AF: 0.565 AC: 8643 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1287 AN: 3468

East Asian (EAS) AF: 0.619 AC: 3198 AN: 5166

South Asian (SAS) AF: 0.543 AC: 2619 AN: 4820

European-Finnish (FIN) AF: 0.446 AC: 4722 AN: 10582

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.451 AC: 30636 AN: 67992

Other (OTH) AF: 0.538 AC: 1139 AN: 2116

Alfa AF: 0.468 Hom.: 19197

Bravo AF: 0.557

Asia WGS AF: 0.583 AC: 2028 AN: 3478

EpiCase AF: 0.450

EpiControl AF: 0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	11
DANN	Benign	0.75
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs216250; hg19: chr12-311949; COSMIC: COSV62885759; COSMIC: COSV62885759;