dbSNP rs2292334: SLC22A3:p.Ala411Ala (chr6-160437156-G-A) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_021977.4(SLC22A3):c.1233G>A(p.Ala411Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,838 control chromosomes in the GnomAD database, including 111,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.30 ( 8067 hom., cov: 32)

Exomes 𝑓: 0.37 ( 103669 hom. )

Consequence

SLC22A3
NM_021977.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.61

Publications

70 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-160437156-G-A is Benign according to our data. Variant chr6-160437156-G-A is described in ClinVar as Benign. ClinVar VariationId is 1264425.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-5.61 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4 link	c.1233G>A	p.Ala411Ala	synonymous_variant	Exon 7 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.1233G>A	p.Ala411Ala	synonymous_variant	Exon 7 of 11	1	NM_021977.4	ENSP00000275300.2		O75751

Frequencies

GnomAD3 genomes

AF:

0.303

AC:

46100

AN:

151964

Hom.:

8055

Cov.:

show subpopulations

Gnomad AFR

AF:

0.138

Gnomad AMI

AF:

0.418

Gnomad AMR

AF:

0.436

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.278

Gnomad FIN

AF:

0.297

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.368

Gnomad OTH

AF:

0.314

GnomAD2 exomes

AF:

0.357

AC:

89650

AN:

251244

AF XY:

0.349

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.520

Gnomad ASJ exome

AF:

0.223

Gnomad EAS exome

AF:

0.445

Gnomad FIN exome

AF:

0.308

Gnomad NFE exome

AF:

0.370

Gnomad OTH exome

AF:

0.341

GnomAD4 exome

AF:

0.370

AC:

541035

AN:

1461756

Hom.:

103669

Cov.:

AF XY:

0.366

AC XY:

266104

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.126

AC:

4206

AN:

33476

American (AMR)

AF:

0.509

AC:

22770

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5805

AN:

26134

East Asian (EAS)

AF:

0.469

AC:

18632

AN:

39700

South Asian (SAS)

AF:

0.277

AC:

23884

AN:

86256

European-Finnish (FIN)

AF:

0.307

AC:

16414

AN:

53418

Middle Eastern (MID)

AF:

0.259

AC:

1492

AN:

5766

European-Non Finnish (NFE)

AF:

0.384

AC:

426911

AN:

1111892

Other (OTH)

AF:

0.346

AC:

20921

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

20763

41526

62288

83051

103814

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13402

26804

40206

53608

67010

<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:

0.303

AC:

46128

AN:

152082

Hom.:

8067

Cov.:

AF XY:

0.301

AC XY:

22386

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.137

AC:

5701

AN:

41512

American (AMR)

AF:

0.437

AC:

6677

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

754

AN:

3472

East Asian (EAS)

AF:

0.462

AC:

2387

AN:

5164

South Asian (SAS)

AF:

0.278

AC:

1336

AN:

4814

European-Finnish (FIN)

AF:

0.297

AC:

3142

AN:

10586

Middle Eastern (MID)

AF:

0.282

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.368

AC:

25000

AN:

67942

Other (OTH)

AF:

0.317

AC:

668

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1561

3122

4682

6243

7804

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

464

928

1392

1856

2320

<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:

0.347

Hom.:

46523

Bravo

AF:

0.309

Asia WGS

AF:

0.383

AC:

1330

AN:

3478

EpiCase

AF:

0.349

EpiControl

AF:

0.345

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 09, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.28

(source)

DANN

Benign

0.69

PhyloP100

-5.6

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over