Genetic Variant SLC22A13:p.Arg16His (chr3-38265907-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.47G>A(p.Arg16His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,614,044 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0058 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0078 ( 50 hom. )

Consequence

SLC22A13
NM_004256.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.247

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=0.0147848725).

BP6

Variant 3-38265907-G-A is Benign according to our data. Variant chr3-38265907-G-A is described in ClinVar as [Benign]. Clinvar id is 2653669.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A13	NM_004256.4 link	c.47G>A	p.Arg16His	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.47G>A	p.Arg16His	missense_variant	Exon 1 of 10	1	NM_004256.4	ENSP00000310241.3		Q9Y226-1
SLC22A13	ENST00000415844.1 link	n.2G>A		non_coding_transcript_exon_variant	Exon 1 of 7	2		ENSP00000395106.1		H0Y4Y1

Frequencies

GnomAD3 genomes

AF:

0.00583

AC:

887

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00135

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00589

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00358

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00566

AC:

1423

AN:

251448

Hom.:

AF XY:

0.00567

AC XY:

771

AN XY:

135890

show subpopulations

Gnomad AFR exome

AF:

0.00148

Gnomad AMR exome

AF:

0.00292

Gnomad ASJ exome

AF:

0.00159

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00383

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00783

AC:

11441

AN:

1461786

Hom.:

Cov.:

AF XY:

0.00765

AC XY:

5566

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00297

Gnomad4 ASJ exome

AF:

0.00168

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00457

Gnomad4 NFE exome

AF:

0.00956

Gnomad4 OTH exome

AF:

0.00566

GnomAD4 genome

AF:

0.00583

AC:

887

AN:

152258

Hom.:

Cov.:

AF XY:

0.00501

AC XY:

373

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00135

Gnomad4 AMR

AF:

0.00588

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00358

Gnomad4 NFE

AF:

0.0101

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00846

Hom.:

Bravo

AF:

0.00553

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00934

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00977

AC:

ExAC

AF:

0.00609

AC:

740

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00829

EpiControl

AF:

0.00723

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SLC22A13: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.32

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.64

MetaRNN

Benign

0.015

MetaSVM

Benign

-1.0

MutationAssessor

Pathogenic

3.1

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.14

Sift

Benign

0.46

Sift4G

Benign

0.60

Polyphen

0.11

Vest4

0.36

MVP

0.44

MPC

0.099

ClinPred

0.022

GERP RS

1.6

Varity_R

0.049

gMVP

0.44

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