rs316244

Variant names:

• chr6-160375533-G-A
• rs316244
• NM_021977.4:c.430-22446G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.430-22446G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,804 control chromosomes in the GnomAD database, including 5,094 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 0.25 (5094 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459
• Publications: 9 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]

ENSG00000287656 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.430-22446G>A		intron_variant	Intron 1 of 10	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.430-22446G>A		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2
ENSG00000287656	ENST00000663900.1	n.1100-5087C>T		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37971 AN: 151686 Hom.: 5091 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.294

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.250 AC: 37991 AN: 151804 Hom.: 5094 Cov.: 32 AF XY: 0.253 AC XY: 18790 AN XY: 74216

African (AFR) AF: 0.166 AC: 6850 AN: 41318

American (AMR) AF: 0.197 AC: 2999 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.353 AC: 1224 AN: 3468

East Asian (EAS) AF: 0.372 AC: 1925 AN: 5172

South Asian (SAS) AF: 0.373 AC: 1796 AN: 4820

European-Finnish (FIN) AF: 0.294 AC: 3088 AN: 10516

Middle Eastern (MID) AF: 0.271 AC: 79 AN: 292

European-Non Finnish (NFE) AF: 0.284 AC: 19282 AN: 67942

Other (OTH) AF: 0.270 AC: 569 AN: 2106

Alfa AF: 0.275 Hom.: 10136

Bravo AF: 0.239

Asia WGS AF: 0.358 AC: 1244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.70
DANN	Benign	0.18
PhyloP100		-0.46
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: rs316244; hg19: chr6-160796565;