Variant chr6-160136611-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_003057.3(SLC22A1):c.1022C>T(p.Pro341Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0262 in 1,614,104 control chromosomes in the GnomAD database, including 1,326 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 0.037 ( 173 hom., cov: 32)

Exomes 𝑓: 0.025 ( 1153 hom. )

Consequence

SLC22A1
NM_003057.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.28

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=0.0045109093).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
SLC22A1	NM_003057.3 linkuse as main transcript	c.1022C>T	p.Pro341Leu	missense_variant	6/11	ENST00000366963.9
SLC22A1	NM_153187.2 linkuse as main transcript	c.1022C>T	p.Pro341Leu	missense_variant	6/10
SLC22A1	XM_005267103.3 linkuse as main transcript	c.1022C>T	p.Pro341Leu	missense_variant	6/12
SLC22A1	XM_006715552.3 linkuse as main transcript	c.1022C>T	p.Pro341Leu	missense_variant	6/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A1	ENST00000366963.9 linkuse as main transcript	c.1022C>T	p.Pro341Leu	missense_variant	6/11	1	NM_003057.3	P1	O15245-1

Frequencies

GnomAD3 genomes

AF:

0.0366

AC:

5562

AN:

152164

Hom.:

173

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0669

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0363

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.124

Gnomad SAS

AF:

0.0837

Gnomad FIN

AF:

0.00810

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0253

GnomAD3 exomes

AF:

0.0376

AC:

9464

AN:

251482

Hom.:

375

AF XY:

0.0377

AC XY:

5123

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.0671

Gnomad AMR exome

AF:

0.0448

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.132

Gnomad SAS exome

AF:

0.0753

Gnomad FIN exome

AF:

0.00878

Gnomad NFE exome

AF:

0.0153

Gnomad OTH exome

AF:

0.0262

GnomAD4 exome

AF:

0.0251

AC:

36665

AN:

1461822

Hom.:

1153

Cov.:

AF XY:

0.0263

AC XY:

19135

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.0691

Gnomad4 AMR exome

AF:

0.0434

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.0735

Gnomad4 FIN exome

AF:

0.00921

Gnomad4 NFE exome

AF:

0.0161

Gnomad4 OTH exome

AF:

0.0263

GnomAD4 genome

AF:

0.0366

AC:

5570

AN:

152282

Hom.:

173

Cov.:

AF XY:

0.0389

AC XY:

2899

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0668

Gnomad4 AMR

AF:

0.0364

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.124

Gnomad4 SAS

AF:

0.0838

Gnomad4 FIN

AF:

0.00810

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0182

Hom.:

108

Bravo

AF:

0.0384

TwinsUK

AF:

0.0165

AC:

ALSPAC

AF:

0.0205

AC:

ESP6500AA

AF:

0.0692

AC:

305

ESP6500EA

AF:

0.0138

AC:

119

ExAC

AF:

0.0384

AC:

4668

Asia WGS

AF:

0.0920

AC:

321

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0161

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.55

D;D;.;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

.;D;D;D

MetaRNN

Benign

0.0045

T;T;T;T

MetaSVM

Uncertain

0.41

MutationAssessor

Pathogenic

3.9

H;H;H;H

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.44

PROVEAN

Pathogenic

-9.2

D;.;D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0010

D;.;D;D

Sift4G

Uncertain

0.0080

D;.;D;D

Polyphen

1.0

D;D;D;.

Vest4

0.28

MPC

0.58

ClinPred

0.10

GERP RS

4.6

Varity_R

0.74

gMVP

0.45

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