Variant rs34059508 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_003057.3(SLC22A1):c.1393G>A(p.Gly465Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0205 in 1,612,278 control chromosomes in the GnomAD database, including 385 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.014 ( 17 hom., cov: 33)

Exomes 𝑓: 0.021 ( 368 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.19

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0138 (2109/152314) while in subpopulation NFE AF= 0.0239 (1625/68028). AF 95% confidence interval is 0.0229. There are 17 homozygotes in gnomad4. There are 959 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 17 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3 link	c.1393G>A	p.Gly465Arg	missense_variant	9/11	ENST00000366963.9	NP_003048.1	O15245-1
SLC22A1	XM_005267103.3 link	c.1393G>A	p.Gly465Arg	missense_variant	9/12		XP_005267160.1
SLC22A1	NM_153187.2 link	c.1386-1170G>A		intron_variant			NP_694857.1	O15245-2
SLC22A1	XM_006715552.3 link	c.1386-3711G>A		intron_variant			XP_006715615.1	O15245-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9 link	c.1393G>A	p.Gly465Arg	missense_variant	9/11	1	NM_003057.3	ENSP00000355930.4		O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0139

AC:

2109

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00916

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00857

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0239

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.0131

AC:

3291

AN:

250670

Hom.:

AF XY:

0.0129

AC XY:

1752

AN XY:

135454

show subpopulations

Gnomad AFR exome

AF:

0.00425

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.0126

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00694

Gnomad NFE exome

AF:

0.0227

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0212

AC:

30909

AN:

1459964

Hom.:

368

Cov.:

AF XY:

0.0207

AC XY:

15029

AN XY:

726386

show subpopulations

Gnomad4 AFR exome

AF:

0.00365

Gnomad4 AMR exome

AF:

0.00760

Gnomad4 ASJ exome

AF:

0.0114

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00201

Gnomad4 FIN exome

AF:

0.00762

Gnomad4 NFE exome

AF:

0.0255

Gnomad4 OTH exome

AF:

0.0197

GnomAD4 genome

AF:

0.0138

AC:

2109

AN:

152314

Hom.:

Cov.:

AF XY:

0.0129

AC XY:

959

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.00915

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00857

Gnomad4 NFE

AF:

0.0239

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.0212

Hom.:

Bravo

AF:

0.0137

TwinsUK

AF:

0.0191

AC:

ALSPAC

AF:

0.0275

AC:

106

ESP6500AA

AF:

0.00340

AC:

ESP6500EA

AF:

0.0260

AC:

224

ExAC

AF:

0.0131

AC:

1587

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0245

EpiControl

AF:

0.0238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.96

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.73

D;D

Eigen

Pathogenic

0.76

Eigen_PC

Uncertain

0.58

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

.;D

MetaRNN

Benign

0.014

T;T

MetaSVM

Pathogenic

0.81

MutationAssessor

Pathogenic

4.5

H;H

PrimateAI

Uncertain

0.51

PROVEAN

Pathogenic

-6.8

D;.

REVEL

Uncertain

0.55

Sift

Uncertain

0.0060

D;.

Sift4G

Pathogenic

0.0010

D;.

Polyphen

1.0

D;D

Vest4

0.30

MutPred

0.79

Loss of catalytic residue at V466 (P = 0.0308);Loss of catalytic residue at V466 (P = 0.0308);

MPC

0.65

ClinPred

0.090

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.65

gMVP

0.93

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.27

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.27

Position offset: -7

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