Genetic Variant SLC22A2:p.Arg400Ser (chr6-160243653-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_003058.4(SLC22A2):c.1198C>A(p.Arg400Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000132 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00011 ( 1 hom. )

Consequence

SLC22A2
NM_003058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.77

Publications

40 publications found

Variant links:

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) 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. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

SLC22A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.1198C>A	p.Arg400Ser	missense	Exon 7 of 11	NP_003049.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.1198C>A	p.Arg400Ser	missense	Exon 7 of 11	ENSP00000355920.3
SLC22A2	ENST00000486916.5	TSL:3	n.237C>A		non_coding_transcript_exon	Exon 2 of 6
SLC22A2	ENST00000491092.1	TSL:5	n.1095C>A		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes

AF:

0.000355

AC:

AN:

152048

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000773

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00317

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000183

AC:

AN:

251316

AF XY:

0.000133

show subpopulations

Gnomad AFR exome

AF:

0.000738

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00228

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000792

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000109

AC:

159

AN:

1461800

Hom.:

Cov.:

AF XY:

0.0000976

AC XY:

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.000299

AC:

AN:

33474

American (AMR)

AF:

0.0000671

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000585

AC:

AN:

1111940

Other (OTH)

AF:

0.000248

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.000355

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.000771

AC:

AN:

41508

American (AMR)

AF:

0.000196

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00317

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

67994

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00000865

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.000181

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Pathogenic

0.25

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.68

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.061

MetaRNN

Uncertain

0.55

MetaSVM

Uncertain

-0.11

MutationAssessor

Pathogenic

3.2

PhyloP100

6.8

PrimateAI

Uncertain

0.50

PROVEAN

Pathogenic

-5.5

REVEL

Uncertain

0.51

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.046

Polyphen

1.0

Vest4

0.95

MVP

0.78

MPC

0.43

ClinPred

0.32

GERP RS

5.5

Varity_R

0.94

gMVP

0.89

Mutation Taster

=40/60

disease causing

(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