Genetic Variant NM_003058.4:c.808T>G (chr6-160249250-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003058.4(SLC22A2):c.808T>G(p.Ser270Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,605,228 control chromosomes in the GnomAD database, including 644,774 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.89 ( 60187 hom., cov: 33)

Exomes 𝑓: 0.90 ( 584587 hom. )

Consequence

SLC22A2
NM_003058.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.50

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.5864516E-6).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A2	NM_003058.4 link	c.808T>G	p.Ser270Ala	missense_variant	Exon 4 of 11	ENST00000366953.8	NP_003049.2	O15244-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC22A2	ENST00000366953.8 link	c.808T>G	p.Ser270Ala	missense_variant	Exon 4 of 11	1	NM_003058.4	ENSP00000355920.3	O15244-1
SLC22A2	ENST00000366952.1 link	c.745T>G	p.Ser249Ala	missense_variant	Exon 6 of 8	5		ENSP00000355919.1	Q5T7Q5
SLC22A2	ENST00000491092.1 link	n.705T>G		non_coding_transcript_exon_variant	Exon 3 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.888

AC:

135119

AN:

152146

Hom.:

60117

Cov.:

show subpopulations

Gnomad AFR

AF:

0.849

Gnomad AMI

AF:

0.899

Gnomad AMR

AF:

0.917

Gnomad ASJ

AF:

0.854

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.876

Gnomad FIN

AF:

0.941

Gnomad MID

AF:

0.832

Gnomad NFE

AF:

0.901

Gnomad OTH

AF:

0.887

GnomAD3 exomes

AF:

0.898

AC:

219538

AN:

244340

Hom.:

98818

AF XY:

0.898

AC XY:

118608

AN XY:

132122

show subpopulations

Gnomad AFR exome

AF:

0.847

Gnomad AMR exome

AF:

0.948

Gnomad ASJ exome

AF:

0.853

Gnomad EAS exome

AF:

0.873

Gnomad SAS exome

AF:

0.875

Gnomad FIN exome

AF:

0.941

Gnomad NFE exome

AF:

0.898

Gnomad OTH exome

AF:

0.895

GnomAD4 exome

AF:

0.897

AC:

1302811

AN:

1452964

Hom.:

584587

Cov.:

AF XY:

0.896

AC XY:

647892

AN XY:

722780

show subpopulations

Gnomad4 AFR exome

AF:

0.849

Gnomad4 AMR exome

AF:

0.944

Gnomad4 ASJ exome

AF:

0.855

Gnomad4 EAS exome

AF:

0.880

Gnomad4 SAS exome

AF:

0.874

Gnomad4 FIN exome

AF:

0.936

Gnomad4 NFE exome

AF:

0.898

Gnomad4 OTH exome

AF:

0.888

GnomAD4 genome

AF:

0.888

AC:

135250

AN:

152264

Hom.:

60187

Cov.:

AF XY:

0.890

AC XY:

66276

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.849

Gnomad4 AMR

AF:

0.917

Gnomad4 ASJ

AF:

0.854

Gnomad4 EAS

AF:

0.871

Gnomad4 SAS

AF:

0.877

Gnomad4 FIN

AF:

0.941

Gnomad4 NFE

AF:

0.901

Gnomad4 OTH

AF:

0.890

Alfa

AF:

0.896

Hom.:

156017

Bravo

AF:

0.885

TwinsUK

AF:

0.898

AC:

3331

ALSPAC

AF:

0.890

AC:

3430

ESP6500AA

AF:

0.854

AC:

3762

ESP6500EA

AF:

0.892

AC:

7672

ExAC

AF:

0.893

AC:

108454

Asia WGS

AF:

0.895

AC:

3114

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

-0.66

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.23

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.35

T;T

MetaRNN

Benign

0.0000036

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.4

M;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.6

N;N

REVEL

Benign

0.14

Sift

Uncertain

0.022

D;D

Sift4G

Uncertain

0.033

D;T

Polyphen

0.25

B;.

Vest4

0.078

MPC

0.19

ClinPred

0.036

GERP RS

-2.3

Varity_R

0.18

gMVP

0.72

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