dbSNP rs8187724: SLC22A3:c.1073+40A>C (chr6-160436917-A-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_021977.4(SLC22A3):c.1073+40A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,610,746 control chromosomes in the GnomAD database, including 266 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 0.018 ( 32 hom., cov: 32)

Exomes 𝑓: 0.015 ( 234 hom. )

Consequence

SLC22A3
NM_021977.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.166

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0175 (2672/152320) while in subpopulation AFR AF = 0.0264 (1099/41572). AF 95% confidence interval is 0.0251. There are 32 homozygotes in GnomAd4. There are 1207 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 32 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.1073+40A>C		intron	N/A	NP_068812.1	O75751

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.1073+40A>C	intron	N/A	ENSP00000275300.2	O75751
SLC22A3	ENST00000855214.1		c.1163+40A>C	intron	N/A	ENSP00000525273.1
SLC22A3	ENST00000855213.1		c.527+40A>C	intron	N/A	ENSP00000525272.1

Frequencies

GnomAD3 genomes

AF:

0.0175

AC:

2669

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0264

Gnomad AMI

AF:

0.0735

Gnomad AMR

AF:

0.0126

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0178

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0112

AC:

2805

AN:

250888

AF XY:

0.0106

show subpopulations

Gnomad AFR exome

AF:

0.0284

Gnomad AMR exome

AF:

0.00978

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.0155

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.0153

AC:

22368

AN:

1458426

Hom.:

234

Cov.:

AF XY:

0.0150

AC XY:

10917

AN XY:

725834

show subpopulations

African (AFR)

AF:

0.0297

AC:

992

AN:

33420

American (AMR)

AF:

0.0107

AC:

478

AN:

44712

Ashkenazi Jewish (ASJ)

AF:

0.00459

AC:

120

AN:

26118

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39644

South Asian (SAS)

AF:

0.00238

AC:

205

AN:

86204

European-Finnish (FIN)

AF:

0.00257

AC:

137

AN:

53406

Middle Eastern (MID)

AF:

0.00521

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0176

AC:

19546

AN:

1108910

Other (OTH)

AF:

0.0143

AC:

859

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1295

2590

3885

5180

6475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

760

1520

2280

3040

3800

<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:

0.0175

AC:

2672

AN:

152320

Hom.:

Cov.:

AF XY:

0.0162

AC XY:

1207

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0264

AC:

1099

AN:

41572

American (AMR)

AF:

0.0126

AC:

193

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00269

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00188

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0178

AC:

1213

AN:

68024

Other (OTH)

AF:

0.0199

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

136

272

409

545

681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.0187

Hom.:

Bravo

AF:

0.0188

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

(source)

DANN

Benign

0.27

PhyloP100

0.17

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over