rs4709426

chr6-160392295-C-Gchr6-160392295-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.430-5684C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.466 in 152,068 control chromosomes in the GnomAD database, including 16,825 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 0.47 (16825 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.430-5684C>G		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.430-5684C>G		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70881 AN: 151950 Hom.: 16814 Cov.: 32

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.611

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.466 AC: 70917 AN: 152068 Hom.: 16825 Cov.: 32 AF XY: 0.468 AC XY: 34798 AN XY: 74312

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.513

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.470

Alfa AF: 0.334 Hom.: 871

Bravo AF: 0.464

Asia WGS AF: 0.542 AC: 1886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.42
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs4709426; hg19: chr6-160813327; COSMIC: COSV51711519;