rs2076828

Positions:

• chr6-160451754-C-G

Variant summary

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

The NM_021977.4(SLC22A3):​c.*698C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 152,028 control chromosomes in the GnomAD database, including 14,784 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 0.43 (14783 hom., cov: 32)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: SLC22A3 NM_021977.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.*698C>G		3_prime_UTR_variant	11/11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.*698C>G		3_prime_UTR_variant	11/11	1	NM_021977.4	ENSP00000275300	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66050 AN: 151886 Hom.: 14768 Cov.: 32

Gnomad AFR AF: 0.430

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.422

Gnomad OTH AF: 0.458

GnomAD4 exome AF: 0.333 AC: 8 AN: 24 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 AMR exome AF: 0.00

Gnomad4 NFE exome AF: 0.364

GnomAD4 genome AF: 0.435 AC: 66092 AN: 152004 Hom.: 14783 Cov.: 32 AF XY: 0.442 AC XY: 32849 AN XY: 74268

Gnomad4 AFR AF: 0.430

Gnomad4 AMR AF: 0.323

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.535

Gnomad4 SAS AF: 0.610

Gnomad4 FIN AF: 0.521

Gnomad4 NFE AF: 0.422

Gnomad4 OTH AF: 0.457

Alfa AF: 0.432 Hom.: 8291

Bravo AF: 0.417

Asia WGS AF: 0.533 AC: 1852 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.46
DANN	Benign	0.60

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: rs2076828; hg19: chr6-160872786;