NM_001122848.3:c.1326+9C>G

Variant names:

• chr12-196115-G-C
• rs115223250
• NM_001122848.3:c.1326+9C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.31
• Publications: 0 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 -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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 8 Cov.: 33

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

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.: 5 Cov.: 34 AF XY: 0.000438 AC XY: 303 AN XY: 691432

African (AFR) AF: 0.0171 AC: 551 AN: 32160

American (AMR) AF: 0.00101 AC: 36 AN: 35786

Ashkenazi Jewish (ASJ) AF: 0.000914 AC: 23 AN: 25166

East Asian (EAS) AF: 0.0000545 AC: 2 AN: 36692

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48932

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4724

European-Non Finnish (NFE) AF: 0.0000185 AC: 20 AN: 1080500

Other (OTH) AF: 0.00109 AC: 63 AN: 58022

GnomAD4 genome AF: 0.00573 AC: 873 AN: 152328 Hom.: 9 Cov.: 33 AF XY: 0.00506 AC XY: 377 AN XY: 74480

African (AFR) AF: 0.0195 AC: 812 AN: 41578

American (AMR) AF: 0.00196 AC: 30 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68026

Other (OTH) AF: 0.0113 AC: 24 AN: 2116

Alfa AF: 0.000602 Hom.: 0

Bravo AF: 0.00652

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: 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
BayesDel_noAF	Benign	-0.87
CADD	Benign	4.2
DANN	Benign	0.69
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs115223250; hg19: chr12-305281;