rs3123636

chr6-160421505-T-Cchr6-160421505-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+10659T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,102 control chromosomes in the GnomAD database, including 5,319 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 0.24 (5319 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.73

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.975+10659T>C		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.975+10659T>C		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36210 AN: 151984 Hom.: 5321 Cov.: 32

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.329

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.238 AC: 36211 AN: 152102 Hom.: 5319 Cov.: 32 AF XY: 0.234 AC XY: 17422 AN XY: 74348

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.244

Gnomad4 SAS AF: 0.282

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.329

Gnomad4 OTH AF: 0.230

Alfa AF: 0.291 Hom.: 7754

Bravo AF: 0.226

Asia WGS AF: 0.310 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.044
Dann	Benign	0.68

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: rs3123636; hg19: chr6-160842537; COSMIC: COSV51711718;