Genetic Variant SLC22A2:p.Ser270Thr (chr6-160249250-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003058.4(SLC22A2):c.808T>A(p.Ser270Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SLC22A2
NM_003058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

Publications

0 publications found

Variant links:

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

SLC22A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.102986544).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.808T>A	p.Ser270Thr	missense	Exon 4 of 11	NP_003049.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.808T>A	p.Ser270Thr	missense	Exon 4 of 11	ENSP00000355920.3
SLC22A2	ENST00000366952.1	TSL:5	c.745T>A	p.Ser249Thr	missense	Exon 6 of 8	ENSP00000355919.1
SLC22A2	ENST00000491092.1	TSL:5	n.705T>A		non_coding_transcript_exon	Exon 3 of 10

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1454238

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723376

African (AFR)

AF:

0.00

AC:

AN:

33102

American (AMR)

AF:

0.00

AC:

AN:

42964

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25980

East Asian (EAS)

AF:

0.00

AC:

AN:

39370

South Asian (SAS)

AF:

0.00

AC:

AN:

84404

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1109148

Other (OTH)

AF:

0.00

AC:

AN:

60134

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.7

(source)

DANN

Benign

0.088

DEOGEN2

Benign

0.16

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.48

M_CAP

Benign

0.0048

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.56

PhyloP100

2.5

PrimateAI

Benign

0.41

PROVEAN

Benign

1.0

REVEL

Benign

0.099

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.16

MutPred

0.64

Loss of glycosylation at S270 (P = 0.1028)

MVP

0.24

MPC

0.067

ClinPred

0.051

GERP RS

-2.3

Varity_R

0.045

gMVP

0.65

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over