NM_003057.3:c.480G>C

Variant names:

• chr6-160130172-G-C
• rs683369
• NM_003057.3:c.480G>C

Variant summary

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

The NM_003057.3(SLC22A1):​c.480G>C​(p.Leu160Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.797 in 1,613,470 control chromosomes in the GnomAD database, including 515,703 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.85 (55247 hom., cov: 28)
  • Exomes 𝑓: 0.79 (460456 hom.)
• Consequence: SLC22A1 NM_003057.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 139 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=1.0099394E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 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.480G>C	p.Leu160Phe	missense	Exon 2 of 11	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.480G>C	p.Leu160Phe	missense	Exon 2 of 10	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.480G>C	p.Leu160Phe	missense	Exon 2 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.480G>C	p.Leu160Phe	missense	Exon 2 of 11	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.594G>C	p.Leu198Phe	missense	Exon 3 of 12	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.480G>C	p.Leu160Phe	missense	Exon 2 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes AF: 0.849 AC: 128885 AN: 151760 Hom.: 55178 Cov.: 28

Gnomad AFR AF: 0.959

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.877

Gnomad ASJ AF: 0.841

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.841

Gnomad MID AF: 0.892

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.856

GnomAD2 exomes AF: 0.831 AC: 208885 AN: 251410 AF XY: 0.826

Gnomad AFR exome AF: 0.963

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.837

Gnomad EAS exome AF: 0.859

Gnomad FIN exome AF: 0.835

Gnomad NFE exome AF: 0.776

Gnomad OTH exome AF: 0.834

GnomAD4 exome AF: 0.792 AC: 1157684 AN: 1461592 Hom.: 460456 Cov.: 54 AF XY: 0.794 AC XY: 577112 AN XY: 727110

African (AFR) AF: 0.968 AC: 32409 AN: 33470

American (AMR) AF: 0.908 AC: 40615 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 21785 AN: 26136

East Asian (EAS) AF: 0.859 AC: 34088 AN: 39698

South Asian (SAS) AF: 0.850 AC: 73344 AN: 86252

European-Finnish (FIN) AF: 0.833 AC: 44467 AN: 53384

Middle Eastern (MID) AF: 0.891 AC: 5140 AN: 5768

European-Non Finnish (NFE) AF: 0.771 AC: 856724 AN: 1111774

Other (OTH) AF: 0.813 AC: 49112 AN: 60390

GnomAD4 genome AF: 0.849 AC: 129014 AN: 151878 Hom.: 55247 Cov.: 28 AF XY: 0.853 AC XY: 63317 AN XY: 74222

African (AFR) AF: 0.959 AC: 39713 AN: 41404

American (AMR) AF: 0.878 AC: 13399 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.841 AC: 2915 AN: 3468

East Asian (EAS) AF: 0.849 AC: 4368 AN: 5144

South Asian (SAS) AF: 0.845 AC: 4041 AN: 4784

European-Finnish (FIN) AF: 0.841 AC: 8871 AN: 10544

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52909 AN: 67956

Other (OTH) AF: 0.857 AC: 1804 AN: 2106

Alfa AF: 0.790 Hom.: 32847

Bravo AF: 0.858

TwinsUK AF: 0.769 AC: 2852

ALSPAC AF: 0.771 AC: 2970

ESP6500AA AF: 0.951 AC: 4188

ESP6500EA AF: 0.779 AC: 6697

ExAC AF: 0.828 AC: 100508

Asia WGS AF: 0.853 AC: 2967 AN: 3478

EpiCase AF: 0.792

EpiControl AF: 0.786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.30
DANN	Benign	0.12
DEOGEN2	Benign	0.16	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0000010	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.035	N
PhyloP100		-0.013
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.98	N
REVEL	Benign	0.095
Sift	Benign	1.0	T
Sift4G	Benign	0.70	T
Polyphen		0.0040	B
Vest4		0.093
MutPred		0.60		Gain of catalytic residue at L160 (P = 0.091)
MPC		0.14
ClinPred		0.00023	T
GERP RS		1.5
PromoterAI		0.018	Neutral
Varity_R		0.052
gMVP		0.56
Mutation Taster		=99/1	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: rs683369; hg19: chr6-160551204; COSMIC: COSV61452681;