rs216250

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-202783-A-C
• chr12-202783-A-G
• chr12-202783-A-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001122848.3(SLC6A12):​c.447T>G​(p.Thr149Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=0.156 with no splicing effect.

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>G	p.Thr149Thr	synonymous	Exon 5 of 16	NP_001116320.1
	SLC6A12	NM_001122847.3		c.447T>G	p.Thr149Thr	synonymous	Exon 5 of 16	NP_001116319.1
	SLC6A12	NM_001206931.2		c.447T>G	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>G	p.Thr149Thr	synonymous	Exon 5 of 16	ENSP00000508194.1
	SLC6A12	ENST00000359674.8	TSL:1	c.447T>G	p.Thr149Thr	synonymous	Exon 5 of 16	ENSP00000352702.4
	SLC6A12	ENST00000397296.6	TSL:1	c.447T>G	p.Thr149Thr	synonymous	Exon 4 of 15	ENSP00000380464.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461680 Hom.: 0 Cov.: 38 AF XY: 0.00000138 AC XY: 1 AN XY: 727150

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

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

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5734

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111884

Other (OTH) AF: 0.00 AC: 0 AN: 60384

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	11
DANN	Benign	0.74
PhyloP100		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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;