rs2174914

Positions:

• chr6-160442076-G-C
• chr6-160442076-G-T

Variant summary

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

The NM_021977.4(SLC22A3):​c.1289-685G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 152,162 control chromosomes in the GnomAD database, including 5,109 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 0.25 (5109 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.1289-685G>C		intron_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.1289-685G>C		intron_variant		1	NM_021977.4	ENSP00000275300	P1

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37560 AN: 152044 Hom.: 5110 Cov.: 32

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.411

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.276

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.247 AC: 37575 AN: 152162 Hom.: 5109 Cov.: 32 AF XY: 0.250 AC XY: 18618 AN XY: 74380

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.394

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.276

Alfa AF: 0.188 Hom.: 474

Bravo AF: 0.235

Asia WGS AF: 0.385 AC: 1337 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.030
DANN	Benign	0.42

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: rs2174914; hg19: chr6-160863108;