Variant rs8177516 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003058.4(SLC22A2):c.1198C>T(p.Arg400Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000835 in 1,613,962 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 4 hom. )

Consequence

SLC22A2
NM_003058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.77

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.021221578).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A2	NM_003058.4 linkuse as main transcript	c.1198C>T	p.Arg400Cys	missense_variant	7/11	ENST00000366953.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A2	ENST00000366953.8 linkuse as main transcript	c.1198C>T	p.Arg400Cys	missense_variant	7/11	1	NM_003058.4	P1	O15244-1
SLC22A2	ENST00000486916.5 linkuse as main transcript	n.237C>T		non_coding_transcript_exon_variant	2/6	3
SLC22A2	ENST00000491092.1 linkuse as main transcript	n.1095C>T		non_coding_transcript_exon_variant	6/10	5

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

650

AN:

152046

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0146

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00150

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00383

GnomAD3 exomes

AF:

0.00123

AC:

309

AN:

251316

Hom.:

AF XY:

0.00102

AC XY:

139

AN XY:

135818

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.000896

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000475

AC:

695

AN:

1461796

Hom.:

Cov.:

AF XY:

0.000415

AC XY:

302

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.0148

Gnomad4 AMR exome

AF:

0.000962

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000558

Gnomad4 OTH exome

AF:

0.00113

GnomAD4 genome

AF:

0.00429

AC:

653

AN:

152166

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0146

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00379

Alfa

AF:

0.000607

Hom.:

Bravo

AF:

0.00488

ESP6500AA

AF:

0.0148

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00146

AC:

177

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.77

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

MetaRNN

Benign

0.021

MetaSVM

Uncertain

0.0010

MutationAssessor

Pathogenic

3.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Pathogenic

-7.3

REVEL

Uncertain

0.40

Sift

Uncertain

0.027

Sift4G

Uncertain

0.020

Polyphen

0.99

Vest4

0.93

MVP

0.82

MPC

0.30

ClinPred

0.088

GERP RS

5.5

Varity_R

0.73

gMVP

0.83

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over