rs8187724

chr6-160436917-A-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_021977.4(SLC22A3):c.1073+40A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 1,610,746 control chromosomes in the GnomAD database, including 266 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 0.018 (32 hom., cov: 32)
  • Exomes 𝑓: 0.015 (234 hom.)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.166

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0175 (2672/152320) while in subpopulation AFR AF= 0.0264 (1099/41572). AF 95% confidence interval is 0.0251. There are 32 homozygotes in gnomad4. There are 1207 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 31 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.1073+40A>C		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1073+40A>C		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 2669 AN: 152202 Hom.: 31 Cov.: 32

Gnomad AFR AF: 0.0264

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0126

Gnomad ASJ AF: 0.00634

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00188

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0178

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.0112 AC: 2805 AN: 250888 Hom.: 30 AF XY: 0.0106 AC XY: 1441 AN XY: 135624

Gnomad AFR exome AF: 0.0284

Gnomad AMR exome AF: 0.00978

Gnomad ASJ exome AF: 0.00546

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00209

Gnomad FIN exome AF: 0.00314

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.0153 AC: 22368 AN: 1458426 Hom.: 234 Cov.: 31 AF XY: 0.0150 AC XY: 10917 AN XY: 725834

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.0107

Gnomad4 ASJ exome AF: 0.00459

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.00257

Gnomad4 NFE exome AF: 0.0176

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0175 AC: 2672 AN: 152320 Hom.: 32 Cov.: 32 AF XY: 0.0162 AC XY: 1207 AN XY: 74482

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.0126

Gnomad4 ASJ AF: 0.00634

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00188

Gnomad4 NFE AF: 0.0178

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0176 Hom.: 11

Bravo AF: 0.0188

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	1.5
Dann	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8187724; hg19: chr6-160857949;