dbSNP rs8187720: SLC22A3:c.975+12C>T (chr6-160410858-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021977.4(SLC22A3):c.975+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,477,010 control chromosomes in the GnomAD database, including 768 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 0.042 ( 399 hom., cov: 31)

Exomes 𝑓: 0.0072 ( 369 hom. )

Consequence

SLC22A3
NM_021977.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.449

Publications

3 publications found

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4 link	c.975+12C>T		intron_variant	Intron 5 of 10	ENST00000275300.3	NP_068812.1	O75751

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3 link	c.975+12C>T		intron_variant	Intron 5 of 10	1	NM_021977.4	ENSP00000275300.2		O75751

Frequencies

GnomAD3 genomes

AF:

0.0417

AC:

6338

AN:

152000

Hom.:

397

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0219

Gnomad ASJ

AF:

0.0297

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000831

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.0443

Gnomad NFE

AF:

0.00312

Gnomad OTH

AF:

0.0382

GnomAD2 exomes

AF:

0.0146

AC:

3617

AN:

248352

AF XY:

0.0117

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0175

Gnomad ASJ exome

AF:

0.0306

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00351

Gnomad OTH exome

AF:

0.0134

GnomAD4 exome

AF:

0.00717

AC:

9501

AN:

1324892

Hom.:

369

Cov.:

AF XY:

0.00662

AC XY:

4413

AN XY:

666456

show subpopulations

African (AFR)

AF:

0.140

AC:

4358

AN:

31022

American (AMR)

AF:

0.0181

AC:

801

AN:

44318

Ashkenazi Jewish (ASJ)

AF:

0.0329

AC:

827

AN:

25150

East Asian (EAS)

AF:

0.00

AC:

AN:

38844

South Asian (SAS)

AF:

0.000516

AC:

AN:

83346

European-Finnish (FIN)

AF:

0.0000381

AC:

AN:

52540

Middle Eastern (MID)

AF:

0.0320

AC:

170

AN:

5312

European-Non Finnish (NFE)

AF:

0.00240

AC:

2369

AN:

988562

Other (OTH)

AF:

0.0167

AC:

931

AN:

55798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

384

768

1153

1537

1921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

182

364

546

728

910

<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:

0.0418

AC:

6351

AN:

152118

Hom.:

399

Cov.:

AF XY:

0.0400

AC XY:

2978

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.135

AC:

5602

AN:

41454

American (AMR)

AF:

0.0219

AC:

335

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0297

AC:

103

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000832

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.0476

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00312

AC:

212

AN:

68002

Other (OTH)

AF:

0.0378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

287

574

862

1149

1436

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

124

186

248

310

<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:

0.0265

Hom.:

123

Bravo

AF:

0.0479

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.2

(source)

DANN

Benign

0.25

PhyloP100

0.45

Mutation Taster

=100/0

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

Computational scores

Splicing

Publications

Other links and lift over