Variant 11-2909685-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_002555.6(SLC22A18):c.511G>A(p.Gly171Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000575 in 1,390,600 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: not found (cov: 33)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

SLC22A18
NM_002555.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.70

Variant links:

Genes affected

SLC22A18 (HGNC:10964): (solute carrier family 22 member 18) This gene is one of several tumor-suppressing subtransferable fragments located in the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. This gene is imprinted, with preferential expression from the maternal allele. Mutations in this gene have been found in Wilms' tumor and lung cancer. This protein may act as a transporter of organic cations, and have a role in the transport of chloroquine and quinidine-related compounds in kidney. Several alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2015]

SLC22A18 links:

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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, 0.911

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A18	NM_002555.6 linkuse as main transcript	c.511G>A	p.Gly171Ser	missense_variant	5/11	ENST00000649076.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A18	ENST00000649076.2 linkuse as main transcript	c.511G>A	p.Gly171Ser	missense_variant	5/11		NM_002555.6	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000716

AC:

AN:

139678

Hom.:

AF XY:

0.00

AC XY:

AN XY:

77314

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000180

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000575

AC:

AN:

1390600

Hom.:

Cov.:

AF XY:

0.00000873

AC XY:

AN XY:

687320

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000276

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000555

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000904

AC:

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

Dec 20, 2023

The c.511G>A (p.G171S) alteration is located in exon 5 (coding exon 4) of the SLC22A18 gene. This alteration results from a G to A substitution at nucleotide position 511, causing the glycine (G) at amino acid position 171 to be replaced by a serine (S). 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

Uncertain

0.44

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

-0.010

Cadd

Uncertain

Dann

Uncertain

0.99

DEOGEN2

Benign

0.22

T;T;T;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.90

M_CAP

Benign

0.049

MetaRNN

Pathogenic

0.91

D;D;D;D

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.9

M;M;M;M

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.58

PROVEAN

Pathogenic

-4.4

D;D;.;D

REVEL

Uncertain

0.45

Sift

Uncertain

0.0080

D;D;.;D

Sift4G

Uncertain

0.017

D;D;.;D

Polyphen

0.98

D;D;D;D

Vest4

0.78

MutPred

0.83

Gain of glycosylation at G171 (P = 0.0576);Gain of glycosylation at G171 (P = 0.0576);Gain of glycosylation at G171 (P = 0.0576);Gain of glycosylation at G171 (P = 0.0576);

MVP

0.80

MPC

0.54

ClinPred

0.97

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.45

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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