rs2457571

Positions:

• chr6-160413796-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.975+2950T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 152,066 control chromosomes in the GnomAD database, including 30,716 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 0.62 (30716 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.975+2950T>C		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.975+2950T>C		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93631 AN: 151948 Hom.: 30683 Cov.: 32

Gnomad AFR AF: 0.840

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.572

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.672

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.616 AC: 93731 AN: 152066 Hom.: 30716 Cov.: 32 AF XY: 0.619 AC XY: 46016 AN XY: 74322

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.673

Gnomad4 SAS AF: 0.618

Gnomad4 FIN AF: 0.561

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.642

Alfa AF: 0.526 Hom.: 31327

Bravo AF: 0.628

Asia WGS AF: 0.611 AC: 2129 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.69
DANN	Benign	0.46

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: rs2457571; hg19: chr6-160834828;