rs8187718

Positions:

• chr6-160348933-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.429+85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00764 in 1,531,550 control chromosomes in the GnomAD database, including 620 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 0.038 (331 hom., cov: 33)
  • Exomes 𝑓: 0.0043 (289 hom.)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.829

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=-0.66).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.429+85C>T		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.429+85C>T		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.0378 AC: 5749 AN: 152184 Hom.: 330 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.00576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.000955

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.00431 AC: 5940 AN: 1379248 Hom.: 289 Cov.: 34 AF XY: 0.00377 AC XY: 2562 AN XY: 680450

Gnomad4 AFR exome AF: 0.133

Gnomad4 AMR exome AF: 0.00832

Gnomad4 ASJ exome AF: 0.00331

Gnomad4 EAS exome AF: 0.0000561

Gnomad4 SAS exome AF: 0.000737

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000556

Gnomad4 OTH exome AF: 0.0108

GnomAD4 genome AF: 0.0378 AC: 5758 AN: 152302 Hom.: 331 Cov.: 33 AF XY: 0.0367 AC XY: 2732 AN XY: 74474

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0147

Gnomad4 ASJ AF: 0.00576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000956

Gnomad4 OTH AF: 0.0241

Alfa AF: 0.0280 Hom.: 18

Bravo AF: 0.0427

Asia WGS AF: 0.00866 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	11
DANN	Benign	0.93

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: rs8187718; hg19: chr6-160769965;