Genetic Variant NM_003057.3:c.1201G>A (chr6-160139792-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003057.3(SLC22A1):c.1201G>A(p.Gly401Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,605,600 control chromosomes in the GnomAD database, including 509 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 0.016 ( 24 hom., cov: 27)

Exomes 𝑓: 0.023 ( 485 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Publications

136 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01881957).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0163 (2474/152048) while in subpopulation NFE AF = 0.0274 (1862/67982). AF 95% confidence interval is 0.0264. There are 24 homozygotes in GnomAd4. There are 1175 alleles in the male GnomAd4 subpopulation. Median coverage is 27. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.1201G>A	p.Gly401Ser	missense_variant	Exon 7 of 11	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	NM_153187.2 link	c.1201G>A	p.Gly401Ser	missense_variant	Exon 7 of 10		NP_694857.1	O15245-2
SLC22A1	NM_001437335.1 link	c.1201G>A	p.Gly401Ser	missense_variant	Exon 7 of 9		NP_001424264.1
SLC22A1	XM_005267103.3 link	c.1201G>A	p.Gly401Ser	missense_variant	Exon 7 of 12		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.1201G>A	p.Gly401Ser	missense_variant	Exon 7 of 11	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2473

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00438

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.00859

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0177

GnomAD2 exomes

AF:

0.0161

AC:

3873

AN:

240596

AF XY:

0.0165

show subpopulations

Gnomad AFR exome

AF:

0.00508

Gnomad AMR exome

AF:

0.00858

Gnomad ASJ exome

AF:

0.00660

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.0229

AC:

33236

AN:

1453552

Hom.:

485

Cov.:

AF XY:

0.0225

AC XY:

16277

AN XY:

722818

show subpopulations

African (AFR)

AF:

0.00389

AC:

128

AN:

32880

American (AMR)

AF:

0.00921

AC:

392

AN:

42576

Ashkenazi Jewish (ASJ)

AF:

0.00658

AC:

169

AN:

25686

East Asian (EAS)

AF:

0.00

AC:

AN:

39530

South Asian (SAS)

AF:

0.00281

AC:

238

AN:

84780

European-Finnish (FIN)

AF:

0.0176

AC:

940

AN:

53310

Middle Eastern (MID)

AF:

0.00646

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0272

AC:

30206

AN:

1109054

Other (OTH)

AF:

0.0188

AC:

1126

AN:

60008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1755

3511

5266

7022

8777

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1146

2292

3438

4584

5730

<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:

0.0163

AC:

2474

AN:

152048

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1175

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00437

AC:

181

AN:

41454

American (AMR)

AF:

0.00858

AC:

131

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0101

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00207

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0171

AC:

181

AN:

10564

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0274

AC:

1862

AN:

67982

Other (OTH)

AF:

0.0175

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

115

230

346

461

576

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0223

Hom.:

178

Bravo

AF:

0.0151

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0251

AC:

216

ExAC

AF:

0.0161

AC:

1959

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;D;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

.;D;D;D

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.9

M;M;M;M

PhyloP100

9.3

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.8

D;.;D;D

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Uncertain

0.023

D;.;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.53

MPC

0.60

ClinPred

0.033

GERP RS

5.1

Varity_R

0.84

gMVP

0.71

Mutation Taster

=87/13

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over