rs2048327

chr6-160442500-T-C

Variant summary

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

The NM_021977.4(SLC22A3):c.1289-261T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 152,184 control chromosomes in the GnomAD database, including 7,753 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 0.29 (7753 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.384

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.449 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.1289-261T>C		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1289-261T>C		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43672 AN: 152066 Hom.: 7740 Cov.: 33

Gnomad AFR AF: 0.0839

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.296

Gnomad MID AF: 0.175

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.292

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

GnomAD4 genome AF: 0.287 AC: 43698 AN: 152184 Hom.: 7753 Cov.: 33 AF XY: 0.285 AC XY: 21208 AN XY: 74416

Gnomad4 AFR AF: 0.0837

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.218

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.296

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.295

Alfa AF: 0.353 Hom.: 23098

Bravo AF: 0.290

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	1.1
Dann	Benign	0.62

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: rs2048327; hg19: chr6-160863532; COSMIC: COSV51711838;