Variant 11-64556004-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_018484.4(SLC22A11):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00282 in 1,605,046 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0029 ( 14 hom. )

Consequence

SLC22A11
NM_018484.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0330

Variant links:

Genes affected

SLC22A11 (HGNC:18120): (solute carrier family 22 member 11) The protein encoded by this gene is 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 is found mainly in the kidney and in the placenta, where it may act to prevent potentially harmful organic anions from reaching the fetus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

SLC22A11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01748842).

BP6

Variant 11-64556004-C-T is Benign according to our data. Variant chr11-64556004-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3042024.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A11	NM_018484.4 link	c.5C>T	p.Ala2Val	missense_variant	1/10	ENST00000301891.9	NP_060954.1	Q9NSA0-1
SLC22A11	NM_001307985.2 link	c.5C>T	p.Ala2Val	missense_variant	1/8		NP_001294914.1	Q9NSA0-2
SLC22A11	XM_011545167.2 link	c.-291C>T		5_prime_UTR_variant	1/9		XP_011543469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A11	ENST00000301891.9 link	c.5C>T	p.Ala2Val	missense_variant	1/10	1	NM_018484.4	ENSP00000301891.4		Q9NSA0-1

Frequencies

GnomAD3 genomes

AF:

0.00189

AC:

287

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00452

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00154

AC:

377

AN:

244776

Hom.:

AF XY:

0.00156

AC XY:

207

AN XY:

132610

show subpopulations

Gnomad AFR exome

AF:

0.000801

Gnomad AMR exome

AF:

0.000320

Gnomad ASJ exome

AF:

0.000102

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000331

Gnomad FIN exome

AF:

0.00317

Gnomad NFE exome

AF:

0.00258

Gnomad OTH exome

AF:

0.000997

GnomAD4 exome

AF:

0.00291

AC:

4232

AN:

1452728

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

2035

AN XY:

722556

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.000247

Gnomad4 ASJ exome

AF:

0.0000774

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000233

Gnomad4 FIN exome

AF:

0.00388

Gnomad4 NFE exome

AF:

0.00352

Gnomad4 OTH exome

AF:

0.00174

GnomAD4 genome

AF:

0.00188

AC:

287

AN:

152318

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

128

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00452

Gnomad4 NFE

AF:

0.00310

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.00232

Hom.:

Bravo

AF:

0.00156

TwinsUK

AF:

0.00216

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00361

AC:

ExAC

AF:

0.00148

AC:

180

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00196

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC22A11-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 07, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;T

Eigen

Benign

-0.087

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.58

T;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.017

T;T;T

MetaSVM

Benign

-0.55

MutationAssessor

Pathogenic

3.2

M;M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.6

D;D;D

REVEL

Benign

0.17

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.0030

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.094

MVP

0.81

MPC

0.49

ClinPred

0.059

GERP RS

1.7

Varity_R

0.31

gMVP

0.19

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