NM_021977.4:c.430-5255A>G

Variant names:

• chr6-160392724-A-G
• rs446926
• NM_021977.4:c.430-5255A>G

Variant summary

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

The NM_021977.4(SLC22A3):​c.430-5255A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,964 control chromosomes in the GnomAD database, including 9,039 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 0.34 (9039 hom., cov: 31)
• Consequence: SLC22A3 NM_021977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.766
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A3	NM_021977.4	c.430-5255A>G		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.430-5255A>G		intron_variant	Intron 1 of 10	1	NM_021977.4	ENSP00000275300.2

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51021 AN: 151850 Hom.: 9031 Cov.: 31

Gnomad AFR AF: 0.456

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.232

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.338

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

GnomAD4 genome AF: 0.336 AC: 51061 AN: 151964 Hom.: 9039 Cov.: 31 AF XY: 0.335 AC XY: 24893 AN XY: 74288

African (AFR) AF: 0.456 AC: 18871 AN: 41418

American (AMR) AF: 0.232 AC: 3537 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1327 AN: 3468

East Asian (EAS) AF: 0.371 AC: 1913 AN: 5158

South Asian (SAS) AF: 0.375 AC: 1808 AN: 4816

European-Finnish (FIN) AF: 0.292 AC: 3077 AN: 10550

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.287 AC: 19535 AN: 67968

Other (OTH) AF: 0.338 AC: 713 AN: 2112

Alfa AF: 0.302 Hom.: 9828

Bravo AF: 0.338

Asia WGS AF: 0.374 AC: 1298 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.76
PhyloP100		0.77
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: rs446926; hg19: chr6-160813756;