Genetic Variant SLC6A12:p.Thr149Thr (chr12-202783-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.156

Publications

24 publications found

Variant links:

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]

SLC6A12 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A12	NM_001122848.3 link	c.447T>C	p.Thr149Thr	synonymous_variant	Exon 5 of 16	ENST00000684302.1	NP_001116320.1	P48065

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A12	ENST00000684302.1 link	c.447T>C	p.Thr149Thr	synonymous_variant	Exon 5 of 16		NM_001122848.3	ENSP00000508194.1		P48065

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

82456

AN:

152016

Hom.:

23375

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.466

AC XY:

338611

AN XY:

726794

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

16985

33971

50956

67942

84927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15084

30168

45252

60336

75420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.543

AC:

82537

AN:

152134

Hom.:

23402

Cov.:

AF XY:

0.545

AC XY:

40533

AN XY:

74352

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1895

3790

5684

7579

9474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over