rs8187720

Positions:

• chr6-160410858-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.975+12C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 1,477,010 control chromosomes in the GnomAD database, including 768 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 0.042 (399 hom., cov: 31)
  • Exomes 𝑓: 0.0072 (369 hom.)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.449

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.975+12C>T		intron_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.975+12C>T		intron_variant		1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6338 AN: 152000 Hom.: 397 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.0297

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000831

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.00312

Gnomad OTH AF: 0.0382

GnomAD3 exomes AF: 0.0146 AC: 3617 AN: 248352 Hom.: 164 AF XY: 0.0117 AC XY: 1578 AN XY: 134358

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.0175

Gnomad ASJ exome AF: 0.0306

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000691

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.00717 AC: 9501 AN: 1324892 Hom.: 369 Cov.: 20 AF XY: 0.00662 AC XY: 4413 AN XY: 666456

Gnomad4 AFR exome AF: 0.140

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0329

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000516

Gnomad4 FIN exome AF: 0.0000381

Gnomad4 NFE exome AF: 0.00240

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.0418 AC: 6351 AN: 152118 Hom.: 399 Cov.: 31 AF XY: 0.0400 AC XY: 2978 AN XY: 74394

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0219

Gnomad4 ASJ AF: 0.0297

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.0000944

Gnomad4 NFE AF: 0.00312

Gnomad4 OTH AF: 0.0378

Alfa AF: 0.0275 Hom.: 86

Bravo AF: 0.0479

Asia WGS AF: 0.00549 AC: 19 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.25

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: rs8187720; hg19: chr6-160831890;