Variant 11-63297311-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_001039752.4(SLC22A10):c.515G>A(p.Arg172Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,605,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SLC22A10
NM_001039752.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.22

Variant links:

Genes affected

SLC22A10 (HGNC:18057): (solute carrier family 22 member 10) Predicted to enable transmembrane transporter activity. Predicted to be involved in organic anion transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC22A10 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.91

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A10	NM_001039752.4 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	3/10	ENST00000332793.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A10	ENST00000332793.11 linkuse as main transcript	c.515G>A	p.Arg172Gln	missense_variant	3/10	1	NM_001039752.4	P1	Q63ZE4-1

Frequencies

GnomAD3 genomes

AF:

0.000164

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000128

AC:

AN:

241452

Hom.:

AF XY:

0.000122

AC XY:

AN XY:

130854

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000183

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000113

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000467

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.000171

GnomAD4 exome

AF:

0.000126

AC:

183

AN:

1452950

Hom.:

Cov.:

AF XY:

0.000123

AC XY:

AN XY:

722388

show subpopulations

Gnomad4 AFR exome

AF:

0.000151

Gnomad4 AMR exome

AF:

0.000210

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000505

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000137

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000164

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000723

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000159

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000356

AC:

ExAC

AF:

0.000107

AC:

EpiCase

AF:

0.0000549

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 18, 2023

The c.515G>A (p.R172Q) alteration is located in exon 3 (coding exon 3) of the SLC22A10 gene. This alteration results from a G to A substitution at nucleotide position 515, causing the arginine (R) at amino acid position 172 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Uncertain

0.074

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.50

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Benign

0.57

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.037

MetaRNN

Pathogenic

0.91

MetaSVM

Pathogenic

0.90

MutationAssessor

Pathogenic

4.2

MutationTaster

Benign

1.0

D;D;N;N

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-3.8

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0010

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MVP

0.54

MPC

0.12

ClinPred

0.90

GERP RS

3.3

Varity_R

0.91

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

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