Variant 11-62993328-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_004254.4(SLC22A8):c.1538G>A(p.Arg513Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00218 in 1,613,878 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0030 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 16 hom. )

Consequence

SLC22A8
NM_004254.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.00

Variant links:

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

SLC22A8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6

Variant 11-62993328-C-T is Benign according to our data. Variant chr11-62993328-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2641897.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A8	NM_004254.4 linkuse as main transcript	c.1538G>A	p.Arg513Gln	missense_variant	11/11	ENST00000336232.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A8	ENST00000336232.7 linkuse as main transcript	c.1538G>A	p.Arg513Gln	missense_variant	11/11	1	NM_004254.4	P1	Q8TCC7-1

Frequencies

GnomAD3 genomes

AF:

0.00299

AC:

454

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0124

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00432

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00269

AC:

674

AN:

250340

Hom.:

AF XY:

0.00264

AC XY:

358

AN XY:

135388

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000232

Gnomad ASJ exome

AF:

0.00289

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.0112

Gnomad NFE exome

AF:

0.00338

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00209

AC:

3061

AN:

1461688

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1601

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00279

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00996

Gnomad4 NFE exome

AF:

0.00210

Gnomad4 OTH exome

AF:

0.00162

GnomAD4 genome

AF:

0.00298

AC:

454

AN:

152190

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

250

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0124

Gnomad4 NFE

AF:

0.00432

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.00151

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00281

AC:

341

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00311

EpiControl

AF:

0.00172

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

SLC22A8: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.076

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.69

Cadd

Benign

7.7

Dann

Benign

0.59

DEOGEN2

Benign

0.068

T;.;.;T

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0029

MetaRNN

Benign

0.0041

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.34

N;.;.;N

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.19

PROVEAN

Benign

0.050

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

0.32

T;T;T;T

Sift4G

Benign

0.64

T;T;T;T

Polyphen

0.0070

B;.;.;B

Vest4

0.055

MVP

0.22

MPC

0.39

ClinPred

0.010

GERP RS

-11

Varity_R

0.020

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.57

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.57

Position offset: -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