dbSNP rs59711975: SLC22A3:c.-151C>G (chr6-160348269-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.-151C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 936,078 control chromosomes in the GnomAD database, including 12 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 0.0068 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00056 ( 3 hom. )

Consequence

SLC22A3
NM_021977.4 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.324

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:

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=-0.77).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00677 (1021/150772) while in subpopulation AFR AF = 0.0234 (967/41354). AF 95% confidence interval is 0.0222. There are 9 homozygotes in GnomAd4. There are 498 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4 link	c.-151C>G		upstream_gene_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3 link	c.-151C>G		upstream_gene_variant		1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes

AF:

0.00675

AC:

1017

AN:

150664

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0234

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00251

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000890

Gnomad OTH

AF:

0.00436

GnomAD4 exome

AF:

0.000556

AC:

437

AN:

785306

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

193

AN XY:

375474

show subpopulations

African (AFR)

AF:

0.0209

AC:

342

AN:

16370

American (AMR)

AF:

0.00223

AC:

AN:

6732

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

10916

East Asian (EAS)

AF:

0.00

AC:

AN:

21192

South Asian (SAS)

AF:

0.000138

AC:

AN:

14450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19870

Middle Eastern (MID)

AF:

0.000446

AC:

AN:

2244

European-Non Finnish (NFE)

AF:

0.0000363

AC:

AN:

661252

Other (OTH)

AF:

0.00164

AC:

AN:

32280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

101

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00677

AC:

1021

AN:

150772

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

498

AN XY:

73646

show subpopulations

African (AFR)

AF:

0.0234

AC:

967

AN:

41354

American (AMR)

AF:

0.00251

AC:

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.000290

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5124

South Asian (SAS)

AF:

0.00

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10202

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000890

AC:

AN:

67414

Other (OTH)

AF:

0.00432

AC:

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

148

198

247

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

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:

0.00423

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

(source)

DANN

Benign

0.71

PhyloP100

-0.32

PromoterAI

0.18

Neutral

(source)

Mutation Taster

=300/0

polymorphism

(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