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

Variant summary

Our verdict is Benign. Variant got -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. 15/20 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 3770493.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A13	NM_004256.4 link	c.305G>A	p.Arg102His	missense_variant	Exon 1 of 10	ENST00000311856.9	NP_004247.2	Q9Y226-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A13	ENST00000311856.9 link	c.305G>A	p.Arg102His	missense_variant	Exon 1 of 10	1	NM_004256.4	ENSP00000310241.3		Q9Y226-1
SLC22A13	ENST00000415844.1 link	n.260G>A		non_coding_transcript_exon_variant	Exon 1 of 7	2		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

GnomAD3 exomes

AF:

0.00644

AC:

1618

AN:

251098

Hom.:

AF XY:

0.00659

AC XY:

894

AN XY:

135722

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 SAS exome

AF:

0.00399

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

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.000803

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00438

Gnomad4 FIN exome

AF:

0.0160

Gnomad4 NFE exome

AF:

0.00848

Gnomad4 OTH exome

AF:

0.00584

GnomAD4 genome

AF:

0.00592

AC:

901

AN:

152268

Hom.:

Cov.:

AF XY:

0.00584

AC XY:

435

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00539

Gnomad4 FIN

AF:

0.0185

Gnomad4 NFE

AF:

0.00873

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.00775

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC22A13: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

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

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

Varity_R

0.036

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over