6-160348779-C-T

Position:

• chr6-160348779-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_021977.4(SLC22A3):​c.360C>T​(p.Arg120=) 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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.360C>T	p.Arg120=	synonymous_variant	1/11	ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.360C>T	p.Arg120=	synonymous_variant	1/11	1	NM_021977.4	P1

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

GnomAD3 exomes AF: 0.447 AC: 70984 AN: 158702 Hom.: 16322 AF XY: 0.447 AC XY: 39143 AN XY: 87572

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 SAS exome AF: 0.374

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

Gnomad4 AFR exome AF: 0.582

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.546

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.368

Gnomad4 FIN exome AF: 0.496

Gnomad4 NFE exome AF: 0.475

Gnomad4 OTH exome AF: 0.463

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

Gnomad4 AFR AF: 0.576

Gnomad4 AMR AF: 0.424

Gnomad4 ASJ AF: 0.552

Gnomad4 EAS AF: 0.300

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.496

Gnomad4 NFE AF: 0.484

Gnomad4 OTH AF: 0.486

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.91

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

Publications

LitVar

Other links and lift over

dbSNP: rs668871; hg19: chr6-160769811; COSMIC: COSV51711307;