Variant rs34130495 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_003057.3(SLC22A1):c.1201G>A(p.Gly401Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0222 in 1,605,600 control chromosomes in the GnomAD database, including 509 homozygotes. In-silico tool predicts 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 0.016 ( 24 hom., cov: 27)

Exomes 𝑓: 0.023 ( 485 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

SLC22A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01881957).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2474/152048) while in subpopulation NFE AF= 0.0274 (1862/67982). AF 95% confidence interval is 0.0264. There are 24 homozygotes in gnomad4. There are 1175 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 24 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC22A1	NM_003057.3 linkuse as main transcript	c.1201G>A	p.Gly401Ser	missense_variant	7/11	ENST00000366963.9
SLC22A1	NM_153187.2 linkuse as main transcript	c.1201G>A	p.Gly401Ser	missense_variant	7/10
SLC22A1	XM_005267103.3 linkuse as main transcript	c.1201G>A	p.Gly401Ser	missense_variant	7/12
SLC22A1	XM_006715552.3 linkuse as main transcript	c.1201G>A	p.Gly401Ser	missense_variant	7/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9 linkuse as main transcript	c.1201G>A	p.Gly401Ser	missense_variant	7/11	1	NM_003057.3	P1	O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2473

AN:

151930

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00438

Gnomad AMI

AF:

0.0396

Gnomad AMR

AF:

0.00859

Gnomad ASJ

AF:

0.0101

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00187

Gnomad FIN

AF:

0.0171

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0274

Gnomad OTH

AF:

0.0177

GnomAD3 exomes

AF:

0.0161

AC:

3873

AN:

240596

Hom.:

AF XY:

0.0165

AC XY:

2152

AN XY:

130116

show subpopulations

Gnomad AFR exome

AF:

0.00508

Gnomad AMR exome

AF:

0.00858

Gnomad ASJ exome

AF:

0.00660

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00269

Gnomad FIN exome

AF:

0.0192

Gnomad NFE exome

AF:

0.0262

Gnomad OTH exome

AF:

0.0161

GnomAD4 exome

AF:

0.0229

AC:

33236

AN:

1453552

Hom.:

485

Cov.:

AF XY:

0.0225

AC XY:

16277

AN XY:

722818

show subpopulations

Gnomad4 AFR exome

AF:

0.00389

Gnomad4 AMR exome

AF:

0.00921

Gnomad4 ASJ exome

AF:

0.00658

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00281

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.0272

Gnomad4 OTH exome

AF:

0.0188

GnomAD4 genome

AF:

0.0163

AC:

2474

AN:

152048

Hom.:

Cov.:

AF XY:

0.0158

AC XY:

1175

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00437

Gnomad4 AMR

AF:

0.00858

Gnomad4 ASJ

AF:

0.0101

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.0171

Gnomad4 NFE

AF:

0.0274

Gnomad4 OTH

AF:

0.0175

Alfa

AF:

0.0232

Hom.:

Bravo

AF:

0.0151

TwinsUK

AF:

0.0267

AC:

ALSPAC

AF:

0.0291

AC:

112

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.0251

AC:

216

ExAC

AF:

0.0161

AC:

1959

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;D;.;.

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Uncertain

0.97

LIST_S2

Pathogenic

0.98

.;D;D;D

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Pathogenic

0.83

MutationAssessor

Uncertain

2.9

M;M;M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.45

PROVEAN

Pathogenic

-5.8

D;.;D;D

REVEL

Uncertain

0.64

Sift

Pathogenic

0.0

D;.;D;D

Sift4G

Uncertain

0.023

D;.;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.53

MPC

0.60

ClinPred

0.033

GERP RS

5.1

Varity_R

0.84

gMVP

0.71

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