Genetic Variant SLC22A13:p.Arg102His (chr3-38266165-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004256.4(SLC22A13):c.305G>A(p.Arg102His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00748 in 1,614,144 control chromosomes in the GnomAD database, including 79 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0059 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 75 hom. )

Consequence

SLC22A13
NM_004256.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.86

Publications

12 publications found

Variant links:

Genes affected

SLC22A13 (HGNC:8494): (solute carrier family 22 member 13) This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 4. The encoded protein is a transmembrane protein involved in the transport of small molecules. This protein can function to mediate urate uptake and is a high affinity nicotinate exchanger in the kidneys and the intestine. [provided by RefSeq, Sep 2008]

SLC22A13 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003730327).

BP6

Variant 3-38266165-G-A is Benign according to our data. Variant chr3-38266165-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3770493.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004256.4. 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
	SLC22A13	NM_004256.4	MANE Select	c.305G>A	p.Arg102His	missense	Exon 1 of 10	NP_004247.2	Q9Y226-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A13	ENST00000311856.9	TSL:1 MANE Select	c.305G>A	p.Arg102His	missense	Exon 1 of 10	ENSP00000310241.3	Q9Y226-1
	SLC22A13	ENST00000415844.1	TSL:2	n.260G>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000395106.1	H0Y4Y1

Frequencies

GnomAD3 genomes

AF:

0.00592

AC:

900

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00538

Gnomad FIN

AF:

0.0185

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00872

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00644

AC:

1618

AN:

251098

AF XY:

0.00659

show subpopulations

Gnomad AFR exome

AF:

0.000678

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.000993

Gnomad EAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.0161

Gnomad NFE exome

AF:

0.00916

Gnomad OTH exome

AF:

0.00473

GnomAD4 exome

AF:

0.00764

AC:

11168

AN:

1461876

Hom.:

Cov.:

AF XY:

0.00764

AC XY:

5559

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33480

American (AMR)

AF:

0.00154

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.000803

AC:

AN:

26136

East Asian (EAS)

AF:

0.000227

AC:

AN:

39700

South Asian (SAS)

AF:

0.00438

AC:

378

AN:

86258

European-Finnish (FIN)

AF:

0.0160

AC:

857

AN:

53410

Middle Eastern (MID)

AF:

0.00225

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00848

AC:

9434

AN:

1112008

Other (OTH)

AF:

0.00584

AC:

353

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

696

1393

2089

2786

3482

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.00592

AC:

901

AN:

152268

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74438

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41544

American (AMR)

AF:

0.00170

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5184

South Asian (SAS)

AF:

0.00539

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0185

AC:

196

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00873

AC:

594

AN:

68020

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00744

Hom.:

Bravo

AF:

0.00445

TwinsUK

AF:

0.00809

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00709

AC:

ExAC

AF:

0.00698

AC:

847

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00791

EpiControl

AF:

0.00735

ClinVar

ClinVar submissions

Significance:Likely 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

0.077

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.015

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.36

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.63

MetaRNN

Benign

0.0037

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.7

PhyloP100

2.9

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.60

REVEL

Benign

0.060

Sift

Benign

0.25

Sift4G

Benign

0.10

Polyphen

0.014

Vest4

0.049

MVP

0.53

MPC

0.095

ClinPred

0.012

GERP RS

1.8

PromoterAI

-0.030

Neutral

(source)

Varity_R

0.036

gMVP

0.60

Mutation Taster

=98/2

polymorphism

(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