rs272893

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

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

Publications

97 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

GnomAD2 exomes

AF:

0.579

AC:

145387

AN:

251158

AF XY:

0.565

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 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

African (AFR)

AF:

0.747

AC:

24969

AN:

33408

American (AMR)

AF:

0.684

AC:

30576

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.604

AC:

15760

AN:

26106

East Asian (EAS)

AF:

0.344

AC:

13651

AN:

39658

South Asian (SAS)

AF:

0.388

AC:

33451

AN:

86160

European-Finnish (FIN)

AF:

0.500

AC:

26677

AN:

53384

Middle Eastern (MID)

AF:

0.537

AC:

3092

AN:

5758

European-Non Finnish (NFE)

AF:

0.628

AC:

696429

AN:

1108374

Other (OTH)

AF:

0.596

AC:

35927

AN:

60262

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15140

30280

45421

60561

75701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18458

36916

55374

73832

92290

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.629

AC:

95625

AN:

152124

Hom.:

30893

Cov.:

AF XY:

0.618

AC XY:

45921

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.744

AC:

30849

AN:

41488

American (AMR)

AF:

0.659

AC:

10075

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.590

AC:

2049

AN:

3470

East Asian (EAS)

AF:

0.351

AC:

1818

AN:

5184

South Asian (SAS)

AF:

0.374

AC:

1804

AN:

4822

European-Finnish (FIN)

AF:

0.495

AC:

5235

AN:

10572

Middle Eastern (MID)

AF:

0.537

AC:

158

AN:

294

European-Non Finnish (NFE)

AF:

0.612

AC:

41607

AN:

67990

Other (OTH)

AF:

0.632

AC:

1336

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1761

3521

5282

7042

8803

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

772

1544

2316

3088

3860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.615

Hom.:

100470

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

(source)

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

PhyloP100

2.3

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

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over