rs8187716

Positions:

• chr6-160348671-C-A
• chr6-160348671-C-G
• chr6-160348671-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_021977.4(SLC22A3):​c.252C>A​(p.Pro84=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000233 in 1,507,098 control chromosomes in the GnomAD database, including 2 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 0.0012 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: SLC22A3 NM_021977.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.37

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP7: Synonymous conserved (PhyloP=-2.37 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.252C>A	p.Pro84=	synonymous_variant	1/11	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.252C>A	p.Pro84=	synonymous_variant	1/11	1	NM_021977.4	ENSP00000275300	P1

Frequencies

GnomAD3 genomes AF: 0.00110 AC: 167 AN: 152086 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00350

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.000241 AC: 25 AN: 103636 Hom.: 0 AF XY: 0.000121 AC XY: 7 AN XY: 57926

Gnomad AFR exome AF: 0.00694

Gnomad AMR exome AF: 0.000567

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000518

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000129 AC: 175 AN: 1354904 Hom.: 1 Cov.: 66 AF XY: 0.000115 AC XY: 77 AN XY: 668100

Gnomad4 AFR exome AF: 0.00456

Gnomad4 AMR exome AF: 0.000548

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000656

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000468

Gnomad4 OTH exome AF: 0.000336

GnomAD4 genome AF: 0.00116 AC: 176 AN: 152194 Hom.: 1 Cov.: 33 AF XY: 0.00103 AC XY: 77 AN XY: 74426

Gnomad4 AFR AF: 0.00371

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000946

Alfa AF: 0.000143 Hom.: 0

Bravo AF: 0.00138

Asia WGS AF: 0.00116 AC: 4 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	4.2
DANN	Benign	0.83

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: rs8187716; hg19: chr6-160769703;