rs3106164

Variant names:

• chr6-160429241-C-T
• rs3106164
• NM_021977.4:c.976-7539C>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.976-7539C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,138 control chromosomes in the GnomAD database, including 5,921 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 (5921 hom., cov: 33)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0400
• Publications: 23 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.976-7539C>T		intron_variant	Intron 5 of 10	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.976-7539C>T		intron_variant	Intron 5 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37887 AN: 152020 Hom.: 5925 Cov.: 33

Gnomad AFR AF: 0.0675

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.316

Gnomad SAS AF: 0.265

Gnomad FIN AF: 0.285

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.249 AC: 37883 AN: 152138 Hom.: 5921 Cov.: 33 AF XY: 0.245 AC XY: 18198 AN XY: 74366

African (AFR) AF: 0.0673 AC: 2794 AN: 41512

American (AMR) AF: 0.248 AC: 3802 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 751 AN: 3466

East Asian (EAS) AF: 0.315 AC: 1631 AN: 5178

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4818

European-Finnish (FIN) AF: 0.285 AC: 3009 AN: 10570

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23681 AN: 67970

Other (OTH) AF: 0.247 AC: 522 AN: 2114

Alfa AF: 0.308 Hom.: 11053

Bravo AF: 0.236

Asia WGS AF: 0.326 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.6
DANN	Benign	0.68
PhyloP100		-0.040
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: rs3106164; hg19: chr6-160850273; COSMIC: COSV51711769;