Genetic Variant SLC22A3:c.-173C>G (chr6-160348247-C-G) – 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.-173C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00408 in 741,014 control chromosomes in the GnomAD database, including 82 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 0.014 ( 65 hom., cov: 33)

Exomes 𝑓: 0.0015 ( 17 hom. )

Consequence

SLC22A3
NM_021977.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.87

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=-0.8).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0143 (2165/150934) while in subpopulation AFR AF = 0.049 (2028/41376). AF 95% confidence interval is 0.0472. There are 65 homozygotes in GnomAd4. There are 1012 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 65 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.-173C>G		upstream_gene	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.-173C>G	upstream_gene	N/A	ENSP00000275300.2	O75751
SLC22A3	ENST00000855214.1		c.-173C>G	upstream_gene	N/A	ENSP00000525273.1
SLC22A3	ENST00000855213.1		c.-173C>G	upstream_gene	N/A	ENSP00000525272.1

Frequencies

GnomAD3 genomes

AF:

0.0142

AC:

2142

AN:

150826

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00594

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.0116

GnomAD4 exome

AF:

0.00146

AC:

859

AN:

590080

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

383

AN XY:

284790

show subpopulations

African (AFR)

AF:

0.0493

AC:

610

AN:

12366

American (AMR)

AF:

0.00352

AC:

AN:

5680

Ashkenazi Jewish (ASJ)

AF:

0.000682

AC:

AN:

8804

East Asian (EAS)

AF:

0.00

AC:

AN:

17812

South Asian (SAS)

AF:

0.00

AC:

AN:

10326

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17798

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

1772

European-Non Finnish (NFE)

AF:

0.000243

AC:

119

AN:

490640

Other (OTH)

AF:

0.00402

AC:

100

AN:

24882

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

115

154

192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.0143

AC:

2165

AN:

150934

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1012

AN XY:

73750

show subpopulations

African (AFR)

AF:

0.0490

AC:

2028

AN:

41376

American (AMR)

AF:

0.00594

AC:

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.000289

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5106

South Asian (SAS)

AF:

0.00

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10142

Middle Eastern (MID)

AF:

0.0171

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000252

AC:

AN:

67594

Other (OTH)

AF:

0.0115

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

104

208

313

417

521

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00197

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.6

(source)

DANN

Benign

0.75

PhyloP100

-1.9

PromoterAI

0.011

Neutral

(source)

Splicing

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