chr6-160443726-A-G

Variant names:

• chr6-160443726-A-G
• rs8187722
• NM_021977.4:c.1494A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_021977.4(SLC22A3):​c.1494A>G​(p.Leu498Leu) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 27 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.1494A>G	p.Leu498Leu	synonymous	Exon 9 of 11	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.1494A>G	p.Leu498Leu	synonymous	Exon 9 of 11	ENSP00000275300.2

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

GnomAD2 exomes AF: 0.00347 AC: 866 AN: 249216 AF XY: 0.00283

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 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

African (AFR) AF: 0.0362 AC: 1207 AN: 33326

American (AMR) AF: 0.00449 AC: 199 AN: 44368

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 45 AN: 26050

East Asian (EAS) AF: 0.00 AC: 0 AN: 39622

South Asian (SAS) AF: 0.000176 AC: 15 AN: 85102

European-Finnish (FIN) AF: 0.0000377 AC: 2 AN: 53076

Middle Eastern (MID) AF: 0.0499 AC: 287 AN: 5750

European-Non Finnish (NFE) AF: 0.000750 AC: 831 AN: 1108670

Other (OTH) AF: 0.00497 AC: 299 AN: 60176

GnomAD4 genome AF: 0.0103 AC: 1563 AN: 152288 Hom.: 27 Cov.: 33 AF XY: 0.0104 AC XY: 775 AN XY: 74464

African (AFR) AF: 0.0317 AC: 1317 AN: 41544

American (AMR) AF: 0.00680 AC: 104 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00115 AC: 4 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.00118 AC: 80 AN: 68034

Other (OTH) AF: 0.0132 AC: 28 AN: 2114

Alfa AF: 0.00511 Hom.: 27

Bravo AF: 0.0119

Asia WGS AF: 0.00347 AC: 12 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	5.7
DANN	Benign	0.79
PhyloP100		1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

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