rs440962

Variant names:

• chr6-160390122-G-A
• rs440962
• NM_021977.4:c.430-7857G>A

Variant summary

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

The NM_021977.4(SLC22A3):​c.430-7857G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,088 control chromosomes in the GnomAD database, including 5,088 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 0.25 (5088 hom., cov: 32)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0130
• Publications: 7 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]

LOC124901453 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.430-7857G>A		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.430-7857G>A		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37976 AN: 151970 Hom.: 5085 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.374

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.269

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

GnomAD4 genome AF: 0.250 AC: 37995 AN: 152088 Hom.: 5088 Cov.: 32 AF XY: 0.253 AC XY: 18795 AN XY: 74328

African (AFR) AF: 0.165 AC: 6845 AN: 41474

American (AMR) AF: 0.196 AC: 3000 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.371 AC: 1916 AN: 5166

South Asian (SAS) AF: 0.374 AC: 1802 AN: 4820

European-Finnish (FIN) AF: 0.293 AC: 3093 AN: 10564

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.284 AC: 19288 AN: 67986

Other (OTH) AF: 0.270 AC: 570 AN: 2114

Alfa AF: 0.273 Hom.: 15853

Bravo AF: 0.239

Asia WGS AF: 0.358 AC: 1242 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.4
DANN	Benign	0.59
PhyloP100		-0.013
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: rs440962; hg19: chr6-160811154;