rs539958

Variant names:

• chr6-160351810-C-T
• rs539958
• NM_021977.4:c.429+2962C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021977.4(SLC22A3):​c.429+2962C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,966 control chromosomes in the GnomAD database, including 19,423 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 0.50 (19423 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.706
• Publications: 21 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.429+2962C>T		intron_variant	Intron 1 of 10	ENST00000275300.3	NP_068812.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A3	ENST00000275300.3	c.429+2962C>T		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.501 AC: 76106 AN: 151846 Hom.: 19387 Cov.: 32

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.381

Gnomad AMR AF: 0.430

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.497

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.492

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

GnomAD4 genome AF: 0.501 AC: 76196 AN: 151966 Hom.: 19423 Cov.: 32 AF XY: 0.498 AC XY: 37013 AN XY: 74252

African (AFR) AF: 0.590 AC: 24447 AN: 41430

American (AMR) AF: 0.429 AC: 6558 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1913 AN: 3466

East Asian (EAS) AF: 0.301 AC: 1553 AN: 5164

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4816

European-Finnish (FIN) AF: 0.497 AC: 5231 AN: 10532

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.489 AC: 33210 AN: 67970

Other (OTH) AF: 0.492 AC: 1038 AN: 2110

Alfa AF: 0.489 Hom.: 8782

Bravo AF: 0.505

Asia WGS AF: 0.362 AC: 1261 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	0.98
DANN	Benign	0.66
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs539958; hg19: chr6-160772842;