rs9364554

Positions:

• chr6-160412632-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+1786C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,132 control chromosomes in the GnomAD database, including 4,172 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 0.21 (4172 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0390

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.975+1786C>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+1786C>T		intron_variant		1	NM_021977.4	ENSP00000275300	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31817 AN: 152014 Hom.: 4174 Cov.: 32

Gnomad AFR AF: 0.0631

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.216

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.234

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.193

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.209 AC: 31822 AN: 152132 Hom.: 4172 Cov.: 32 AF XY: 0.207 AC XY: 15430 AN XY: 74370

Gnomad4 AFR AF: 0.0632

Gnomad4 AMR AF: 0.216

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.234

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.196

Alfa AF: 0.266 Hom.: 12362

Bravo AF: 0.200

Asia WGS AF: 0.334 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.53

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: rs9364554; hg19: chr6-160833664; COSMIC: COSV51710312;