rs34059508

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1BS2

The NM_003057.3(SLC22A1):c.1393G>A(p.Gly465Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0205 in 1,612,278 control chromosomes in the GnomAD database, including 385 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 0.014 ( 17 hom., cov: 33)

Exomes 𝑓: 0.021 ( 368 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.19

Publications

149 publications found

Variant links:

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]

SLC22A1 links:

ENSG00000301636 (HGNC:):

ENSG00000301636 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0138 (2109/152314) while in subpopulation NFE AF = 0.0239 (1625/68028). AF 95% confidence interval is 0.0229. There are 17 homozygotes in GnomAd4. There are 959 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A1	NM_003057.3	MANE Select	c.1393G>A	p.Gly465Arg	missense	Exon 9 of 11	NP_003048.1	O15245-1
SLC22A1	NM_153187.2		c.1386-1170G>A		intron	N/A	NP_694857.1	O15245-2
SLC22A1	NM_001437335.1		c.1386-3711G>A		intron	N/A	NP_001424264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.1393G>A	p.Gly465Arg	missense	Exon 9 of 11	ENSP00000355930.4	O15245-1
SLC22A1	ENST00000898298.1		c.1507G>A	p.Gly503Arg	missense	Exon 10 of 12	ENSP00000568357.1
SLC22A1	ENST00000898304.1		c.1480G>A	p.Gly494Arg	missense	Exon 10 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2109

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.00907

GnomAD2 exomes

AF:

0.0131

AC:

3291

AN:

250670

AF XY:

0.0129

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0212

AC:

30909

AN:

1459964

Hom.:

368

Cov.:

AF XY:

0.0207

AC XY:

15029

AN XY:

726386

show subpopulations

African (AFR)

AF:

0.00365

AC:

122

AN:

33440

American (AMR)

AF:

0.00760

AC:

339

AN:

44624

Ashkenazi Jewish (ASJ)

AF:

0.0114

AC:

298

AN:

26114

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39674

South Asian (SAS)

AF:

0.00201

AC:

173

AN:

86108

European-Finnish (FIN)

AF:

0.00762

AC:

407

AN:

53412

Middle Eastern (MID)

AF:

0.00314

AC:

AN:

5740

European-Non Finnish (NFE)

AF:

0.0255

AC:

28361

AN:

1110526

Other (OTH)

AF:

0.0197

AC:

1188

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

1278

2556

3834

5112

6390

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1028

2056

3084

4112

5140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0138

AC:

2109

AN:

152314

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

959

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.00402

AC:

167

AN:

41562

American (AMR)

AF:

0.00915

AC:

140

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00893

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00249

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00857

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0239

AC:

1625

AN:

68028

Other (OTH)

AF:

0.00898

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

106

212

319

425

531

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0202

Hom.:

Bravo

AF:

0.0137

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0275

AC:

106

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0260

AC:

224

ExAC

AF:

0.0131

AC:

1587

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

MetaRNN

Benign

0.014

MetaSVM

Pathogenic

0.81

MutationAssessor

Pathogenic

4.5

PhyloP100

4.2

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.8

REVEL

Uncertain

0.55

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.30

MutPred

0.79

Loss of catalytic residue at V466 (P = 0.0308)

MPC

0.65

ClinPred

0.090

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.93

Mutation Taster

=87/13

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: -7

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over