rs2292334

Variant names:

• chr6-160437156-G-A
• rs2292334
• NM_021977.4:c.1233G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-160437156-G-A
• chr6-160437156-G-C
• chr6-160437156-G-T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_021977.4(SLC22A3):​c.1233G>A​(p.Ala411Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,838 control chromosomes in the GnomAD database, including 111,736 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.30 (8067 hom., cov: 32)
  • Exomes 𝑓: 0.37 (103669 hom.)
• Consequence: SLC22A3 NM_021977.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -5.61
• Publications: 70 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 6-160437156-G-A is Benign according to our data. Variant chr6-160437156-G-A is described in ClinVar as Benign. ClinVar VariationId is 1264425.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-5.61 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	NM_021977.4	MANE Select	c.1233G>A	p.Ala411Ala	synonymous	Exon 7 of 11	NP_068812.1	O75751

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.1233G>A	p.Ala411Ala	synonymous	Exon 7 of 11	ENSP00000275300.2	O75751
	SLC22A3	ENST00000855214.1		c.1323G>A	p.Ala441Ala	synonymous	Exon 8 of 12	ENSP00000525273.1
	SLC22A3	ENST00000855213.1		c.687G>A	p.Ala229Ala	synonymous	Exon 3 of 7	ENSP00000525272.1

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46100 AN: 151964 Hom.: 8055 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.368

Gnomad OTH AF: 0.314

GnomAD2 exomes AF: 0.357 AC: 89650 AN: 251244 AF XY: 0.349

Gnomad AFR exome AF: 0.128

Gnomad AMR exome AF: 0.520

Gnomad ASJ exome AF: 0.223

Gnomad EAS exome AF: 0.445

Gnomad FIN exome AF: 0.308

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.341

GnomAD4 exome AF: 0.370 AC: 541035 AN: 1461756 Hom.: 103669 Cov.: 61 AF XY: 0.366 AC XY: 266104 AN XY: 727204

African (AFR) AF: 0.126 AC: 4206 AN: 33476

American (AMR) AF: 0.509 AC: 22770 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5805 AN: 26134

East Asian (EAS) AF: 0.469 AC: 18632 AN: 39700

South Asian (SAS) AF: 0.277 AC: 23884 AN: 86256

European-Finnish (FIN) AF: 0.307 AC: 16414 AN: 53418

Middle Eastern (MID) AF: 0.259 AC: 1492 AN: 5766

European-Non Finnish (NFE) AF: 0.384 AC: 426911 AN: 1111892

Other (OTH) AF: 0.346 AC: 20921 AN: 60392

GnomAD4 genome AF: 0.303 AC: 46128 AN: 152082 Hom.: 8067 Cov.: 32 AF XY: 0.301 AC XY: 22386 AN XY: 74338

African (AFR) AF: 0.137 AC: 5701 AN: 41512

American (AMR) AF: 0.437 AC: 6677 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 754 AN: 3472

East Asian (EAS) AF: 0.462 AC: 2387 AN: 5164

South Asian (SAS) AF: 0.278 AC: 1336 AN: 4814

European-Finnish (FIN) AF: 0.297 AC: 3142 AN: 10586

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.368 AC: 25000 AN: 67942

Other (OTH) AF: 0.317 AC: 668 AN: 2110

Alfa AF: 0.347 Hom.: 46523

Bravo AF: 0.309

Asia WGS AF: 0.383 AC: 1330 AN: 3478

EpiCase AF: 0.349

EpiControl AF: 0.345

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.28
DANN	Benign	0.69
PhyloP100		-5.6
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: rs2292334; hg19: chr6-160858188; COSMIC: COSV51709980;