rs9457925

Positions:

• chr6-160427711-G-A

Variant summary

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

The NM_021977.4(SLC22A3):​c.976-9069G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 152,318 control chromosomes in the GnomAD database, including 302 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 0.032 (302 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.166 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.976-9069G>A		intron_variant		ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.976-9069G>A		intron_variant		1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.0320 AC: 4865 AN: 152200 Hom.: 289 Cov.: 32

Gnomad AFR AF: 0.00878

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.170

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0901

Gnomad SAS AF: 0.00456

Gnomad FIN AF: 0.00970

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0435

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

GnomAD4 genome AF: 0.0321 AC: 4891 AN: 152318 Hom.: 302 Cov.: 32 AF XY: 0.0334 AC XY: 2484 AN XY: 74478

Gnomad4 AFR AF: 0.00875

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0903

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.00970

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0430

Alfa AF: 0.0322 Hom.: 314

Bravo AF: 0.0464

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.63
DANN	Benign	0.52

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: rs9457925; hg19: chr6-160848743;