6-160429879-C-T

Variant summary

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

The NM_021977.4(SLC22A3):c.976-6901C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,544 control chromosomes in the GnomAD database, including 5,419 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 (5419 hom., cov: 31)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.458

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A3	NM_021977.4	c.976-6901C>T		intron_variant		ENST00000275300.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A3	ENST00000275300.3	c.976-6901C>T		intron_variant		1	NM_021977.4	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39569 AN: 151440 Hom.: 5419 Cov.: 31

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.360

Gnomad SAS AF: 0.390

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.291

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

GnomAD4 genome AF: 0.261 AC: 39585 AN: 151544 Hom.: 5419 Cov.: 31 AF XY: 0.265 AC XY: 19589 AN XY: 74028

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.352

Gnomad4 EAS AF: 0.360

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.298

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.292

Alfa AF: 0.277 Hom.: 6263

Bravo AF: 0.253

Asia WGS AF: 0.366 AC: 1270 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.2
Dann	Benign	0.59

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: rs2661834; hg19: chr6-160850911;