rs394468

Variant names:

• chr6-160359880-G-T
• rs394468
• NM_021977.4:c.429+11032G>T

Variant summary

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

The NM_021977.4(SLC22A3):​c.429+11032G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 151,084 control chromosomes in the GnomAD database, including 5,600 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 0.27 (5600 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.429+11032G>T		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.429+11032G>T		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41017 AN: 150964 Hom.: 5586 Cov.: 33

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.250

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.279

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.272 AC: 41072 AN: 151084 Hom.: 5600 Cov.: 33 AF XY: 0.271 AC XY: 20010 AN XY: 73906

African (AFR) AF: 0.277 AC: 11201 AN: 40504

American (AMR) AF: 0.201 AC: 3065 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1587 AN: 5180

South Asian (SAS) AF: 0.251 AC: 1211 AN: 4826

European-Finnish (FIN) AF: 0.285 AC: 3014 AN: 10566

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18970 AN: 67962

Other (OTH) AF: 0.283 AC: 595 AN: 2100

Alfa AF: 0.272 Hom.: 7412

Bravo AF: 0.266

Asia WGS AF: 0.294 AC: 1019 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.7
DANN	Benign	0.68
PhyloP100		0.17
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: rs394468; hg19: chr6-160780912;