rs8187722

chr6-160443726-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.77

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]

ACMG classification

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. Median coverage is 33. 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
SLC22A3	NM_021977.4	c.1494A>G	p.Leu498=	synonymous_variant	9/11	ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1494A>G	p.Leu498=	synonymous_variant	9/11	1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1564 AN: 152174 Hom.: 28 Cov.: 33

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

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

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

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

Other links and lift over

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