Genetic Variant SLC6A12:c.1326+9C>G (chr12-196115-G-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001122848.3(SLC6A12):c.1326+9C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00101 in 1,553,890 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 5 hom. )

Consequence

SLC6A12
NM_001122848.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.31

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 12-196115-G-C is Benign according to our data. Variant chr12-196115-G-C is described in ClinVar as Benign. ClinVar VariationId is 787548.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00573 (873/152328) while in subpopulation AFR AF = 0.0195 (812/41578). AF 95% confidence interval is 0.0184. There are 9 homozygotes in GnomAd4. There are 377 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A12	NM_001122848.3	MANE Select	c.1326+9C>G	intron	N/A	NP_001116320.1	P48065
SLC6A12	NM_001122847.3		c.1326+9C>G	intron	N/A	NP_001116319.1	P48065
SLC6A12	NM_001206931.2		c.1326+9C>G	intron	N/A	NP_001193860.1	P48065

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC6A12	ENST00000684302.1	MANE Select	c.1326+9C>G	intron	N/A	ENSP00000508194.1	P48065
SLC6A12	ENST00000359674.8	TSL:1	c.1326+9C>G	intron	N/A	ENSP00000352702.4	P48065
SLC6A12	ENST00000397296.6	TSL:1	c.1326+9C>G	intron	N/A	ENSP00000380464.2	P48065

Frequencies

GnomAD3 genomes

AF:

0.00568

AC:

864

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0196

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00669

GnomAD2 exomes

AF:

0.00140

AC:

225

AN:

160666

AF XY:

0.000895

show subpopulations

Gnomad AFR exome

AF:

0.0205

Gnomad AMR exome

AF:

0.000765

Gnomad ASJ exome

AF:

0.000823

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000798

Gnomad OTH exome

AF:

0.000888

GnomAD4 exome

AF:

0.000497

AC:

696

AN:

1401562

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

303

AN XY:

691432

show subpopulations

African (AFR)

AF:

0.0171

AC:

551

AN:

32160

American (AMR)

AF:

0.00101

AC:

AN:

35786

Ashkenazi Jewish (ASJ)

AF:

0.000914

AC:

AN:

25166

East Asian (EAS)

AF:

0.0000545

AC:

AN:

36692

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79580

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48932

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4724

European-Non Finnish (NFE)

AF:

0.0000185

AC:

AN:

1080500

Other (OTH)

AF:

0.00109

AC:

AN:

58022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00573

AC:

873

AN:

152328

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

377

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.0195

AC:

812

AN:

41578

American (AMR)

AF:

0.00196

AC:

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68026

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000602

Hom.:

Bravo

AF:

0.00652

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.2

(source)

DANN

Benign

0.69

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over