6-160357607-C-T

Variant names:

• chr6-160357607-C-T
• rs394487
• NM_021977.4:c.429+8759C>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+8759C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 151,946 control chromosomes in the GnomAD database, including 10,557 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 0.35 (10557 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.499
• Publications: 9 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 = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.429+8759C>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+8759C>T		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53590 AN: 151828 Hom.: 10525 Cov.: 32

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.238

Gnomad ASJ AF: 0.368

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.286

Gnomad MID AF: 0.402

Gnomad NFE AF: 0.283

Gnomad OTH AF: 0.354

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

GnomAD4 genome AF: 0.353 AC: 53676 AN: 151946 Hom.: 10557 Cov.: 32 AF XY: 0.349 AC XY: 25923 AN XY: 74246

African (AFR) AF: 0.546 AC: 22634 AN: 41432

American (AMR) AF: 0.238 AC: 3628 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.368 AC: 1277 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1585 AN: 5174

South Asian (SAS) AF: 0.255 AC: 1223 AN: 4804

European-Finnish (FIN) AF: 0.286 AC: 3016 AN: 10538

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.283 AC: 19265 AN: 67964

Other (OTH) AF: 0.355 AC: 749 AN: 2110

Alfa AF: 0.305 Hom.: 27836

Bravo AF: 0.362

Asia WGS AF: 0.314 AC: 1093 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	2.4
DANN	Benign	0.64
PhyloP100		-0.50
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: rs394487; hg19: chr6-160778639;