rs3088442

Positions:

• chr6-160451620-G-A
• chr6-160451620-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.*564G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 157,666 control chromosomes in the GnomAD database, including 8,171 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 0.29 (7757 hom., cov: 32)
  • Exomes 𝑓: 0.37 (414 hom.)
• Consequence: SLC22A3 NM_021977.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.*564G>A		3_prime_UTR_variant	11/11	ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.*564G>A		3_prime_UTR_variant	11/11	1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.288 AC: 43726 AN: 151978 Hom.: 7743 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.418

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.276

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.291

GnomAD4 exome AF: 0.369 AC: 2056 AN: 5570 Hom.: 414 Cov.: 0 AF XY: 0.369 AC XY: 1066 AN XY: 2890

Gnomad4 AFR exome AF: 0.0526

Gnomad4 AMR exome AF: 0.441

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.416

Gnomad4 SAS exome AF: 0.220

Gnomad4 FIN exome AF: 0.231

Gnomad4 NFE exome AF: 0.367

Gnomad4 OTH exome AF: 0.358

GnomAD4 genome AF: 0.288 AC: 43754 AN: 152096 Hom.: 7757 Cov.: 32 AF XY: 0.286 AC XY: 21230 AN XY: 74338

Gnomad4 AFR AF: 0.0858

Gnomad4 AMR AF: 0.431

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.276

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.367

Gnomad4 OTH AF: 0.292

Alfa AF: 0.348 Hom.: 9040

Bravo AF: 0.290

Asia WGS AF: 0.380 AC: 1317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.036
DANN	Benign	0.54

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: rs3088442; hg19: chr6-160872652; COSMIC: COSV51716624; COSMIC: COSV51716624;