rs12208357

Variant names:

• chr6-160122116-C-T
• rs12208357
• NM_003057.3:c.181C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.181C>T​(p.Arg61Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0628 in 1,613,778 control chromosomes in the GnomAD database, including 3,629 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 0.048 (230 hom., cov: 33)
  • Exomes 𝑓: 0.064 (3399 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• Publications: 236 publications found

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0042586923).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. 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
	SLC22A1	NM_003057.3	MANE Select	c.181C>T	p.Arg61Cys	missense	Exon 1 of 11	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.181C>T	p.Arg61Cys	missense	Exon 1 of 10	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.181C>T	p.Arg61Cys	missense	Exon 1 of 9	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.181C>T	p.Arg61Cys	missense	Exon 1 of 11	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.181C>T	p.Arg61Cys	missense	Exon 1 of 12	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.181C>T	p.Arg61Cys	missense	Exon 1 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes AF: 0.0480 AC: 7306 AN: 152246 Hom.: 230 Cov.: 33

Gnomad AFR AF: 0.0108

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.0278

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0252

Gnomad FIN AF: 0.0590

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.0435

GnomAD2 exomes AF: 0.0517 AC: 12989 AN: 251004 AF XY: 0.0529

Gnomad AFR exome AF: 0.00998

Gnomad AMR exome AF: 0.0234

Gnomad ASJ exome AF: 0.0954

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0559

Gnomad NFE exome AF: 0.0761

Gnomad OTH exome AF: 0.0532

GnomAD4 exome AF: 0.0644 AC: 94043 AN: 1461414 Hom.: 3399 Cov.: 32 AF XY: 0.0639 AC XY: 46472 AN XY: 727028

African (AFR) AF: 0.00941 AC: 315 AN: 33480

American (AMR) AF: 0.0249 AC: 1114 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0964 AC: 2518 AN: 26132

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39700

South Asian (SAS) AF: 0.0274 AC: 2362 AN: 86250

European-Finnish (FIN) AF: 0.0571 AC: 3029 AN: 53020

Middle Eastern (MID) AF: 0.0635 AC: 366 AN: 5768

European-Non Finnish (NFE) AF: 0.0728 AC: 80940 AN: 1111966

Other (OTH) AF: 0.0561 AC: 3390 AN: 60380

GnomAD4 genome AF: 0.0479 AC: 7303 AN: 152364 Hom.: 230 Cov.: 33 AF XY: 0.0451 AC XY: 3361 AN XY: 74504

African (AFR) AF: 0.0108 AC: 449 AN: 41590

American (AMR) AF: 0.0276 AC: 422 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 331 AN: 3472

East Asian (EAS) AF: 0.000579 AC: 3 AN: 5184

South Asian (SAS) AF: 0.0257 AC: 124 AN: 4830

European-Finnish (FIN) AF: 0.0590 AC: 627 AN: 10626

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0754 AC: 5131 AN: 68032

Other (OTH) AF: 0.0430 AC: 91 AN: 2116

Alfa AF: 0.0638 Hom.: 629

Bravo AF: 0.0440

TwinsUK AF: 0.0734 AC: 272

ALSPAC AF: 0.0729 AC: 281

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.0808 AC: 695

ExAC AF: 0.0524 AC: 6356

Asia WGS AF: 0.0110 AC: 40 AN: 3478

EpiCase AF: 0.0701

EpiControl AF: 0.0720

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T
Eigen	Benign	0.10
Eigen_PC	Benign	-0.079
FATHMM_MKL	Benign	0.13	N
LIST_S2	Pathogenic	0.98	D
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.54	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.32
PrimateAI	Uncertain	0.51	T
PROVEAN	Pathogenic	-5.6	D
REVEL	Benign	0.28
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.36
MPC		0.70
ClinPred		0.049	T
GERP RS		2.7
PromoterAI		-0.019	Neutral
Varity_R		0.32
gMVP		0.61
Mutation Taster		=94/6	polymorphism (auto)

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: rs12208357; hg19: chr6-160543148; COSMIC: COSV105878488;