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rs8187722

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

The NM_021977.4(SLC22A3):c.1494A>G(p.Leu498=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,608,428 control chromosomes in the GnomAD database, including 84 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 0.010 ( 27 hom., cov: 33)
Exomes 𝑓: 0.0020 ( 57 hom. )

Consequence

SLC22A3
NM_021977.4 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.77
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.28).
BP7
Synonymous conserved (PhyloP=1.77 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1563/152288) while in subpopulation AFR AF= 0.0317 (1317/41544). AF 95% confidence interval is 0.0303. There are 27 homozygotes in gnomad4. There are 775 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAd at 28 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC22A3NM_021977.4 linkuse as main transcriptc.1494A>G p.Leu498= synonymous_variant 9/11 ENST00000275300.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC22A3ENST00000275300.3 linkuse as main transcriptc.1494A>G p.Leu498= synonymous_variant 9/111 NM_021977.4 P1

Frequencies

GnomAD3 genomes
AF:
0.0103
AC:
1564
AN:
152174
Hom.:
28
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0318
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00681
Gnomad ASJ
AF:
0.00115
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0918
Gnomad NFE
AF:
0.00118
Gnomad OTH
AF:
0.0129
GnomAD3 exomes
AF:
0.00347
AC:
866
AN:
249216
Hom.:
11
AF XY:
0.00283
AC XY:
381
AN XY:
134546
show subpopulations
Gnomad AFR exome
AF:
0.0315
Gnomad AMR exome
AF:
0.00371
Gnomad ASJ exome
AF:
0.00140
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000235
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00147
Gnomad OTH exome
AF:
0.00673
GnomAD4 exome
AF:
0.00198
AC:
2885
AN:
1456140
Hom.:
57
Cov.:
29
AF XY:
0.00193
AC XY:
1395
AN XY:
724058
show subpopulations
Gnomad4 AFR exome
AF:
0.0362
Gnomad4 AMR exome
AF:
0.00449
Gnomad4 ASJ exome
AF:
0.00173
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000176
Gnomad4 FIN exome
AF:
0.0000377
Gnomad4 NFE exome
AF:
0.000750
Gnomad4 OTH exome
AF:
0.00497
GnomAD4 genome
AF:
0.0103
AC:
1563
AN:
152288
Hom.:
27
Cov.:
33
AF XY:
0.0104
AC XY:
775
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.0317
Gnomad4 AMR
AF:
0.00680
Gnomad4 ASJ
AF:
0.00115
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000414
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00118
Gnomad4 OTH
AF:
0.0132
Alfa
AF:
0.00345
Hom.:
13
Bravo
AF:
0.0119
Asia WGS
AF:
0.00347
AC:
12
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.28
Cadd
Benign
5.7
Dann
Benign
0.79
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs8187722; hg19: chr6-160864758; COSMIC: COSV99279592; API