rs2457575

Positions:

• chr6-160447295-A-G
• chr6-160447295-A-T

Variant summary

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

The NM_021977.4(SLC22A3):​c.1511-424A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,094 control chromosomes in the GnomAD database, including 5,008 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 0.24 (5008 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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 (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.1511-424A>G		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1511-424A>G		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36872 AN: 151976 Hom.: 5009 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.417

Gnomad SAS AF: 0.391

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.242 AC: 36882 AN: 152094 Hom.: 5008 Cov.: 32 AF XY: 0.246 AC XY: 18296 AN XY: 74330

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.358

Gnomad4 EAS AF: 0.418

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.274

Alfa AF: 0.279 Hom.: 6811

Bravo AF: 0.231

Asia WGS AF: 0.385 AC: 1337 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	7.2
DANN	Benign	0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2457575; hg19: chr6-160868327;