rs555754

chr6-160348391-G-Achr6-160348391-G-Cchr6-160348391-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021977.4(SLC22A3):c.-29G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 1,429,486 control chromosomes in the GnomAD database, including 159,083 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.49 (18343 hom., cov: 34)
  • Exomes 𝑓: 0.47 (140740 hom.)
• Consequence: SLC22A3 NM_021977.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.716

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 6-160348391-G-A is Benign according to our data. Variant chr6-160348391-G-A is described in ClinVar as [Benign]. Clinvar id is 1241019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.-29G>A		5_prime_UTR_variant	1/11	ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.-29G>A		5_prime_UTR_variant	1/11	1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74007 AN: 151460 Hom.: 18309 Cov.: 34

Gnomad AFR AF: 0.556

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.359

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.483

Gnomad OTH AF: 0.481

GnomAD3 exomes AF: 0.468 AC: 43965 AN: 93916 Hom.: 10421 AF XY: 0.472 AC XY: 25237 AN XY: 53460

Gnomad AFR exome AF: 0.574

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.338

Gnomad SAS exome AF: 0.384

Gnomad FIN exome AF: 0.516

Gnomad NFE exome AF: 0.495

Gnomad OTH exome AF: 0.505

GnomAD4 exome AF: 0.467 AC: 596530 AN: 1277916 Hom.: 140740 Cov.: 40 AF XY: 0.466 AC XY: 291202 AN XY: 625548

Gnomad4 AFR exome AF: 0.562

Gnomad4 AMR exome AF: 0.400

Gnomad4 ASJ exome AF: 0.547

Gnomad4 EAS exome AF: 0.299

Gnomad4 SAS exome AF: 0.370

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.463

GnomAD4 genome AF: 0.489 AC: 74093 AN: 151570 Hom.: 18343 Cov.: 34 AF XY: 0.487 AC XY: 36062 AN XY: 74078

Gnomad4 AFR AF: 0.557

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.550

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.495

Gnomad4 NFE AF: 0.483

Gnomad4 OTH AF: 0.480

Alfa AF: 0.435 Hom.: 4551

Bravo AF: 0.490

Asia WGS AF: 0.356 AC: 1209 AN: 3394

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

This variant is associated with the following publications: (PMID: 22231567) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
Cadd	Benign	14
Dann	Benign	0.95
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.3

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: rs555754; hg19: chr6-160769423; COSMIC: COSV51710349;