Variant chr11-64559204-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_018484.4(SLC22A11):c.463G>A(p.Val155Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,611,204 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V155G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0081 ( 13 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 25 hom. )

Consequence

SLC22A11
NM_018484.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.187

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013583392).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00805 (1225/152158) while in subpopulation AFR AF= 0.0265 (1098/41504). AF 95% confidence interval is 0.0252. There are 13 homozygotes in gnomad4. There are 567 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC22A11	NM_018484.4 linkuse as main transcript	c.463G>A	p.Val155Met	missense_variant	2/10	ENST00000301891.9
SLC22A11	NM_001307985.2 linkuse as main transcript	c.463G>A	p.Val155Met	missense_variant	2/8
SLC22A11	XM_011545167.2 linkuse as main transcript	c.99-2800G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A11	ENST00000301891.9 linkuse as main transcript	c.463G>A	p.Val155Met	missense_variant	2/10	1	NM_018484.4	P1	Q9NSA0-1

Frequencies

GnomAD3 genomes

AF:

0.00800

AC:

1217

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0263

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000456

Gnomad OTH

AF:

0.00813

GnomAD3 exomes

AF:

0.00224

AC:

559

AN:

249080

Hom.:

AF XY:

0.00156

AC XY:

210

AN XY:

134580

show subpopulations

Gnomad AFR exome

AF:

0.0257

Gnomad AMR exome

AF:

0.00207

Gnomad ASJ exome

AF:

0.000101

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000657

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000365

Gnomad OTH exome

AF:

0.00198

GnomAD4 exome

AF:

0.00116

AC:

1692

AN:

1459046

Hom.:

Cov.:

AF XY:

0.00112

AC XY:

810

AN XY:

725540

show subpopulations

Gnomad4 AFR exome

AF:

0.0292

Gnomad4 AMR exome

AF:

0.00236

Gnomad4 ASJ exome

AF:

0.0000384

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000616

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000293

Gnomad4 OTH exome

AF:

0.00319

GnomAD4 genome

AF:

0.00805

AC:

1225

AN:

152158

Hom.:

Cov.:

AF XY:

0.00762

AC XY:

567

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0265

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000456

Gnomad4 OTH

AF:

0.00804

Alfa

AF:

0.00348

Hom.:

Bravo

AF:

0.00932

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0268

AC:

118

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.00266

AC:

323

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.29

T;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

N;N;N

REVEL

Benign

0.24

Sift

Benign

0.057

T;D;T

Sift4G

Uncertain

0.030

D;D;T

Polyphen

0.73

P;P;P

Vest4

0.13

MVP

0.70

MPC

0.40

ClinPred

0.0030

GERP RS

-1.4

Varity_R

0.048

gMVP

0.14

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