rs628031

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_003057.3(SLC22A1):c.1222A>G(p.Met408Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 1,565,314 control chromosomes in the GnomAD database, including 293,961 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M408I) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.65 ( 32470 hom., cov: 29)

Exomes 𝑓: 0.61 ( 261491 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.48

Publications

184 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.262719E-7).

BP6

Variant 6-160139813-A-G is Benign according to our data. Variant chr6-160139813-A-G is described in ClinVar as Benign. ClinVar VariationId is 1283709.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.724 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A1	NM_003057.3	MANE Select	c.1222A>G	p.Met408Val	missense	Exon 7 of 11	NP_003048.1	O15245-1
SLC22A1	NM_153187.2		c.1222A>G	p.Met408Val	missense	Exon 7 of 10	NP_694857.1	O15245-2
SLC22A1	NM_001437335.1		c.1222A>G	p.Met408Val	missense	Exon 7 of 9	NP_001424264.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.1222A>G	p.Met408Val	missense	Exon 7 of 11	ENSP00000355930.4	O15245-1
SLC22A1	ENST00000898298.1		c.1336A>G	p.Met446Val	missense	Exon 8 of 12	ENSP00000568357.1
SLC22A1	ENST00000898304.1		c.1222A>G	p.Met408Val	missense	Exon 7 of 12	ENSP00000568363.1

Frequencies

GnomAD3 genomes

AF:

0.651

AC:

98648

AN:

151618

Hom.:

32425

Cov.:

show subpopulations

Gnomad AFR

AF:

0.728

Gnomad AMI

AF:

0.614

Gnomad AMR

AF:

0.735

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.726

Gnomad SAS

AF:

0.628

Gnomad FIN

AF:

0.551

Gnomad MID

AF:

0.747

Gnomad NFE

AF:

0.595

Gnomad OTH

AF:

0.673

GnomAD2 exomes

AF:

0.633

AC:

130245

AN:

205896

AF XY:

0.625

show subpopulations

Gnomad AFR exome

AF:

0.728

Gnomad AMR exome

AF:

0.799

Gnomad ASJ exome

AF:

0.647

Gnomad EAS exome

AF:

0.728

Gnomad FIN exome

AF:

0.545

Gnomad NFE exome

AF:

0.583

Gnomad OTH exome

AF:

0.635

GnomAD4 exome

AF:

0.605

AC:

855332

AN:

1413578

Hom.:

261491

Cov.:

AF XY:

0.606

AC XY:

424000

AN XY:

699724

show subpopulations

African (AFR)

AF:

0.736

AC:

22767

AN:

30930

American (AMR)

AF:

0.794

AC:

27309

AN:

34394

Ashkenazi Jewish (ASJ)

AF:

0.654

AC:

15669

AN:

23952

East Asian (EAS)

AF:

0.756

AC:

28949

AN:

38298

South Asian (SAS)

AF:

0.630

AC:

50610

AN:

80322

European-Finnish (FIN)

AF:

0.547

AC:

28765

AN:

52548

Middle Eastern (MID)

AF:

0.703

AC:

3899

AN:

5548

European-Non Finnish (NFE)

AF:

0.588

AC:

641116

AN:

1089588

Other (OTH)

AF:

0.625

AC:

36248

AN:

57998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

16114

32227

48341

64454

80568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17988

35976

53964

71952

89940

<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:

0.651

AC:

98753

AN:

151736

Hom.:

32470

Cov.:

AF XY:

0.651

AC XY:

48280

AN XY:

74116

show subpopulations

African (AFR)

AF:

0.728

AC:

30127

AN:

41362

American (AMR)

AF:

0.735

AC:

11225

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2306

AN:

3470

East Asian (EAS)

AF:

0.726

AC:

3733

AN:

5140

South Asian (SAS)

AF:

0.627

AC:

3007

AN:

4794

European-Finnish (FIN)

AF:

0.551

AC:

5767

AN:

10474

Middle Eastern (MID)

AF:

0.752

AC:

221

AN:

294

European-Non Finnish (NFE)

AF:

0.595

AC:

40387

AN:

67924

Other (OTH)

AF:

0.676

AC:

1424

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1716

3432

5147

6863

8579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<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:

0.617

Hom.:

138697

Bravo

AF:

0.672

TwinsUK

AF:

0.577

AC:

2141

ALSPAC

AF:

0.607

AC:

2338

ESP6500AA

AF:

0.726

AC:

3200

ESP6500EA

AF:

0.592

AC:

5093

ExAC

AF:

0.638

AC:

77502

Asia WGS

AF:

0.675

AC:

2344

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

0.0020

(source)

DANN

Benign

0.35

DEOGEN2

Benign

0.078

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.21

MetaRNN

Benign

8.3e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.7

PhyloP100

-2.5

PrimateAI

Benign

0.24

PROVEAN

Benign

1.1

REVEL

Benign

0.040

Sift

Benign

1.0

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.018

MPC

0.13

ClinPred

0.030

GERP RS

-9.1

Varity_R

0.032

gMVP

0.15

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over