rs750197629

Variant names:

• chr12-191096-A-G
• rs750197629
• NM_001122848.3:c.1817T>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001122848.3(SLC6A12):​c.1817T>C​(p.Ile606Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000134 in 1,340,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: SLC6A12 NM_001122848.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.89
• 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]

ENSG00000255671 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07509613).

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.1817T>C	p.Ile606Thr	missense	Exon 16 of 16	NP_001116320.1	P48065
	SLC6A12	NM_001122847.3		c.1817T>C	p.Ile606Thr	missense	Exon 16 of 16	NP_001116319.1	P48065
	SLC6A12	NM_001206931.2		c.1817T>C	p.Ile606Thr	missense	Exon 15 of 15	NP_001193860.1	P48065

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A12	ENST00000684302.1	MANE Select	c.1817T>C	p.Ile606Thr	missense	Exon 16 of 16	ENSP00000508194.1	P48065
	SLC6A12	ENST00000359674.8	TSL:1	c.1817T>C	p.Ile606Thr	missense	Exon 16 of 16	ENSP00000352702.4	P48065
	SLC6A12	ENST00000397296.6	TSL:1	c.1817T>C	p.Ile606Thr	missense	Exon 15 of 15	ENSP00000380464.2	P48065

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000258 AC: 3 AN: 116194 AF XY: 0.0000321

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000515

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000143 AC: 17 AN: 1188542 Hom.: 0 Cov.: 30 AF XY: 0.00000698 AC XY: 4 AN XY: 573150

African (AFR) AF: 0.00 AC: 0 AN: 25562

American (AMR) AF: 0.00 AC: 0 AN: 20946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16572

East Asian (EAS) AF: 0.00 AC: 0 AN: 30946

South Asian (SAS) AF: 0.00 AC: 0 AN: 33150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42790

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4800

European-Non Finnish (NFE) AF: 0.0000166 AC: 16 AN: 966138

Other (OTH) AF: 0.0000210 AC: 1 AN: 47638

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152248 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74384

African (AFR) AF: 0.00 AC: 0 AN: 41464

American (AMR) AF: 0.00 AC: 0 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000987 Hom.: 0

Bravo AF: 0.0000227

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.00000828 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.64
DEOGEN2	Benign	0.030	T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.97	L
PhyloP100		1.9
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.57	N
REVEL	Benign	0.21
Sift	Benign	0.094	T
Sift4G	Benign	0.11	T
Polyphen		0.0	B
Vest4		0.088
MVP		0.67
ClinPred		0.068	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.071
gMVP		0.16
Mutation Taster		=95/5	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: rs750197629; hg19: chr12-300262;