NM_021977.4:c.360C>T

Variant names:

• chr6-160348779-C-T
• rs668871
• NM_021977.4:c.360C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021977.4(SLC22A3):​c.360C>T​(p.Arg120Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,556,644 control chromosomes in the GnomAD database, including 172,921 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 0.49 (18910 hom., cov: 34)
  • Exomes 𝑓: 0.47 (154011 hom.)
• Consequence: SLC22A3 NM_021977.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 41 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP7: Synonymous conserved (PhyloP=1.11 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.569 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.360C>T	p.Arg120Arg	synonymous	Exon 1 of 11	NP_068812.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A3	ENST00000275300.3	TSL:1 MANE Select	c.360C>T	p.Arg120Arg	synonymous	Exon 1 of 11	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.495 AC: 75203 AN: 152020 Hom.: 18877 Cov.: 34

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.300

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.487

GnomAD2 exomes AF: 0.447 AC: 70984 AN: 158702 AF XY: 0.447

Gnomad AFR exome AF: 0.588

Gnomad AMR exome AF: 0.384

Gnomad ASJ exome AF: 0.547

Gnomad EAS exome AF: 0.318

Gnomad FIN exome AF: 0.497

Gnomad NFE exome AF: 0.490

Gnomad OTH exome AF: 0.465

GnomAD4 exome AF: 0.465 AC: 653747 AN: 1404508 Hom.: 154011 Cov.: 72 AF XY: 0.463 AC XY: 322144 AN XY: 695088

African (AFR) AF: 0.582 AC: 18912 AN: 32474

American (AMR) AF: 0.391 AC: 15458 AN: 39544

Ashkenazi Jewish (ASJ) AF: 0.546 AC: 13835 AN: 25358

East Asian (EAS) AF: 0.300 AC: 11137 AN: 37154

South Asian (SAS) AF: 0.368 AC: 29659 AN: 80494

European-Finnish (FIN) AF: 0.496 AC: 17447 AN: 35206

Middle Eastern (MID) AF: 0.475 AC: 2586 AN: 5446

European-Non Finnish (NFE) AF: 0.475 AC: 517598 AN: 1090212

Other (OTH) AF: 0.463 AC: 27115 AN: 58620

GnomAD4 genome AF: 0.495 AC: 75289 AN: 152136 Hom.: 18910 Cov.: 34 AF XY: 0.492 AC XY: 36619 AN XY: 74366

African (AFR) AF: 0.576 AC: 23889 AN: 41506

American (AMR) AF: 0.424 AC: 6485 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1915 AN: 3468

East Asian (EAS) AF: 0.300 AC: 1543 AN: 5146

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4824

European-Finnish (FIN) AF: 0.496 AC: 5260 AN: 10608

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32928 AN: 67966

Other (OTH) AF: 0.486 AC: 1026 AN: 2110

Alfa AF: 0.428 Hom.: 2137

Bravo AF: 0.498

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		1.1
PromoterAI		-0.0062	Neutral
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: rs668871; hg19: chr6-160769811; COSMIC: COSV51711307;