rs7745775

chr6-160412436-T-G

Variant summary

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

The NM_021977.4(SLC22A3):c.975+1590T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 152,072 control chromosomes in the GnomAD database, including 5,144 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 0.26 (5144 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.270

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.975+1590T>G		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.975+1590T>G		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38774 AN: 151954 Hom.: 5136 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.327

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.205

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.255 AC: 38804 AN: 152072 Hom.: 5144 Cov.: 32 AF XY: 0.259 AC XY: 19231 AN XY: 74346

Gnomad4 AFR AF: 0.311

Gnomad4 AMR AF: 0.328

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.244

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.205

Gnomad4 OTH AF: 0.272

Alfa AF: 0.217 Hom.: 4252

Bravo AF: 0.262

Asia WGS AF: 0.208 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	11
Dann	Benign	0.84

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: rs7745775; hg19: chr6-160833468;