Variant chr6-160256637-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000366953.8(SLC22A2):c.495G>A(p.Met165Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000276 in 1,613,328 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0016 ( 2 hom., cov: 33)

Exomes 𝑓: 0.00013 ( 1 hom. )

Consequence

SLC22A2
ENST00000366953.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.171

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010011375).

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A2	NM_003058.4 linkuse as main transcript	c.495G>A	p.Met165Ile	missense_variant	2/11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8 linkuse as main transcript	c.495G>A	p.Met165Ile	missense_variant	2/11	1	NM_003058.4	ENSP00000355920	P1	O15244-1
SLC22A2	ENST00000366952.1 linkuse as main transcript	c.432G>A	p.Met144Ile	missense_variant	4/8	5		ENSP00000355919
SLC22A2	ENST00000491092.1 linkuse as main transcript	n.415+1707G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

250

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00577

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.00

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000366

AC:

AN:

251450

Hom.:

AF XY:

0.000258

AC XY:

AN XY:

135898

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.000116

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000134

AC:

196

AN:

1461056

Hom.:

Cov.:

AF XY:

0.000114

AC XY:

AN XY:

726914

show subpopulations

Gnomad4 AFR exome

AF:

0.00496

Gnomad4 AMR exome

AF:

0.000112

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:

0.00000540

Gnomad4 OTH exome

AF:

0.000315

GnomAD4 genome

AF:

0.00164

AC:

250

AN:

152272

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00575

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000269

Hom.:

Bravo

AF:

0.00166

ESP6500AA

AF:

0.00454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000502

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.61

CADD

Benign

2.6

DANN

Benign

0.54

DEOGEN2

Benign

0.089

T;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.83

T;T

M_CAP

Benign

0.0063

MetaRNN

Benign

0.010

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.10

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.21

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.13

Sift

Benign

0.38

T;T

Sift4G

Benign

0.61

T;T

Polyphen

0.0

B;.

Vest4

0.13

MutPred

0.55

Gain of catalytic residue at M165 (P = 0.0184);.;

MVP

0.31

MPC

0.076

ClinPred

0.0064

GERP RS

4.9

Varity_R

0.19

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

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