rs272893

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003059.3(SLC22A4):c.917T>C(p.Ile306Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,609,940 control chromosomes in the GnomAD database, including 302,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.63 ( 30893 hom., cov: 32)

Exomes 𝑓: 0.60 ( 271485 hom. )

Consequence

SLC22A4
NM_003059.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) 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. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

SLC22A4 links:

MIR3936HG (HGNC:40538): (MIR3936 host gene)

MIR3936HG links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=2.2935872E-6).

BP6

Variant 5-132327369-T-C is Benign according to our data. Variant chr5-132327369-T-C is described in ClinVar as [Benign]. Clinvar id is 1270019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3 link	c.917T>C	p.Ile306Thr	missense_variant	Exon 5 of 10	ENST00000200652.4	NP_003050.2	Q9H015

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SLC22A4	ENST00000200652.4 link	c.917T>C	p.Ile306Thr	missense_variant	Exon 5 of 10	1	NM_003059.3	ENSP00000200652.3	Q9H015
MIR3936HG	ENST00000621103.4 link	n.824+4820A>G		intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000425923.1 link	n.447T>C		non_coding_transcript_exon_variant	Exon 3 of 3	3
MIR3936HG	ENST00000669845.1 link	n.450+4820A>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes

AF:

0.629

AC:

95537

AN:

152006

Hom.:

30860

Cov.:

show subpopulations

Gnomad AFR

AF:

0.744

Gnomad AMI

AF:

0.761

Gnomad AMR

AF:

0.660

Gnomad ASJ

AF:

0.590

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.375

Gnomad FIN

AF:

0.495

Gnomad MID

AF:

0.522

Gnomad NFE

AF:

0.612

Gnomad OTH

AF:

0.632

GnomAD3 exomes

AF:

0.579

AC:

145387

AN:

251158

Hom.:

43823

AF XY:

0.565

AC XY:

76655

AN XY:

135742

show subpopulations

Gnomad AFR exome

AF:

0.746

Gnomad AMR exome

AF:

0.692

Gnomad ASJ exome

AF:

0.602

Gnomad EAS exome

AF:

0.375

Gnomad SAS exome

AF:

0.383

Gnomad FIN exome

AF:

0.496

Gnomad NFE exome

AF:

0.619

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.604

AC:

880532

AN:

1457816

Hom.:

271485

Cov.:

AF XY:

0.596

AC XY:

432545

AN XY:

725412

show subpopulations

Gnomad4 AFR exome

AF:

0.747

Gnomad4 AMR exome

AF:

0.684

Gnomad4 ASJ exome

AF:

0.604

Gnomad4 EAS exome

AF:

0.344

Gnomad4 SAS exome

AF:

0.388

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.628

Gnomad4 OTH exome

AF:

0.596

GnomAD4 genome

AF:

0.629

AC:

95625

AN:

152124

Hom.:

30893

Cov.:

AF XY:

0.618

AC XY:

45921

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.744

Gnomad4 AMR

AF:

0.659

Gnomad4 ASJ

AF:

0.590

Gnomad4 EAS

AF:

0.351

Gnomad4 SAS

AF:

0.374

Gnomad4 FIN

AF:

0.495

Gnomad4 NFE

AF:

0.612

Gnomad4 OTH

AF:

0.632

Alfa

AF:

0.612

Hom.:

70022

Bravo

AF:

0.653

TwinsUK

AF:

0.643

AC:

2385

ALSPAC

AF:

0.627

AC:

2416

ESP6500AA

AF:

0.739

AC:

3256

ESP6500EA

AF:

0.615

AC:

5291

ExAC

AF:

0.576

AC:

69972

Asia WGS

AF:

0.403

AC:

1402

AN:

3476

EpiCase

AF:

0.622

EpiControl

AF:

0.630

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.30

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.70

MetaRNN

Benign

0.0000023

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.14

Sift

Benign

0.046

Sift4G

Uncertain

0.035

Polyphen

0.0020

Vest4

0.026

MPC

0.29

ClinPred

0.015

GERP RS

-1.1

Varity_R

0.22

gMVP

0.36

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over