6-160392295-C-G

Variant names:

• chr6-160392295-C-G
• rs4709426
• NM_021977.4:c.430-5684C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

LOC124901453 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021977.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.430-5684C>G		intron	N/A	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.430-5684C>G		intron	N/A	ENSP00000275300.2

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

African (AFR) AF: 0.381 AC: 15799 AN: 41468

American (AMR) AF: 0.546 AC: 8347 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1504 AN: 3470

East Asian (EAS) AF: 0.565 AC: 2913 AN: 5158

South Asian (SAS) AF: 0.513 AC: 2471 AN: 4814

European-Finnish (FIN) AF: 0.502 AC: 5307 AN: 10572

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32902 AN: 67972

Other (OTH) AF: 0.470 AC: 991 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.42
DANN	Benign	0.71
PhyloP100		-1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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