dbSNP rs8187722: SLC22A3:p.Leu498Leu (chr6-160443726-A-G) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_021977.4(SLC22A3):c.1494A>G(p.Leu498Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,608,428 control chromosomes in the GnomAD database, including 84 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.

Frequency

Genomes: 𝑓 0.010 ( 27 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 57 hom. )

Consequence

SLC22A3
NM_021977.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77

Variant links:

Genes affected

SLC22A3 (HGNC:10967): (solute carrier family 22 member 3) 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. [provided by RefSeq, Jul 2008]

SLC22A3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.28).

BP7

Synonymous conserved (PhyloP=1.77 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0103 (1563/152288) while in subpopulation AFR AF = 0.0317 (1317/41544). AF 95% confidence interval is 0.0303. There are 27 homozygotes in GnomAd4. There are 775 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position FAILED quality control check.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4 link	c.1494A>G	p.Leu498Leu	synonymous_variant	Exon 9 of 11	ENST00000275300.3	NP_068812.1	O75751

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3 link	c.1494A>G	p.Leu498Leu	synonymous_variant	Exon 9 of 11	1	NM_021977.4	ENSP00000275300.2		O75751

Frequencies

GnomAD3 genomes

AF:

0.0103

AC:

1564

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0318

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00681

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.00118

Gnomad OTH

AF:

0.0129

GnomAD2 exomes

AF:

0.00347

AC:

866

AN:

249216

AF XY:

0.00283

show subpopulations

Gnomad AFR exome

AF:

0.0315

Gnomad AMR exome

AF:

0.00371

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00147

Gnomad OTH exome

AF:

0.00673

GnomAD4 exome

AF:

0.00198

AC:

2885

AN:

1456140

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1395

AN XY:

724058

show subpopulations

Gnomad4 AFR exome

AF:

0.0362

AC:

1207

AN:

33326

Gnomad4 AMR exome

AF:

0.00449

AC:

199

AN:

44368

Gnomad4 ASJ exome

AF:

0.00173

AC:

AN:

26050

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

39622

Gnomad4 SAS exome

AF:

0.000176

AC:

AN:

85102

Gnomad4 FIN exome

AF:

0.0000377

AC:

AN:

53076

Gnomad4 NFE exome

AF:

0.000750

AC:

831

AN:

1108670

Gnomad4 Remaining exome

AF:

0.00497

AC:

299

AN:

60176

Heterozygous variant carriers

123

246

370

493

616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

120

180

240

300

<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:

0.0103

AC:

1563

AN:

152288

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

775

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.0317

AC:

0.0317013

AN:

0.0317013

Gnomad4 AMR

AF:

0.00680

AC:

0.00679827

AN:

0.00679827

Gnomad4 ASJ

AF:

0.00115

AC:

0.00115274

AN:

0.00115274

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.000414

AC:

0.000414422

AN:

0.000414422

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00118

AC:

0.00117588

AN:

0.00117588

Gnomad4 OTH

AF:

0.0132

AC:

0.013245

AN:

0.013245

Heterozygous variant carriers

158

236

315

394

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00511

Hom.:

Bravo

AF:

0.0119

Asia WGS

AF:

0.00347

AC:

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.28

CADD

Benign

5.7

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

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