rs3219198

Positions:

• chr6-160217161-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003058.4(SLC22A2):​c.*271T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00542 in 324,624 control chromosomes in the GnomAD database, including 13 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 0.0053 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (6 hom.)
• Consequence: SLC22A2 NM_003058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.127

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) 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. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.*271T>C		3_prime_UTR_variant	11/11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8	c.*271T>C		3_prime_UTR_variant	11/11	1	NM_003058.4	ENSP00000355920	P1
SLC22A2	ENST00000498556.1	n.588T>C		non_coding_transcript_exon_variant	3/3	5
SLC22A2	ENST00000486916.5	n.640+7544T>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00530 AC: 807 AN: 152126 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0306

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00481

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00554 AC: 955 AN: 172380 Hom.: 6 Cov.: 0 AF XY: 0.00562 AC XY: 493 AN XY: 87730

Gnomad4 AFR exome AF: 0.00218

Gnomad4 AMR exome AF: 0.00424

Gnomad4 ASJ exome AF: 0.00456

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.0242

Gnomad4 NFE exome AF: 0.00465

Gnomad4 OTH exome AF: 0.00493

GnomAD4 genome AF: 0.00529 AC: 806 AN: 152244 Hom.: 7 Cov.: 32 AF XY: 0.00596 AC XY: 444 AN XY: 74454

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00425

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.0306

Gnomad4 NFE AF: 0.00481

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00468 Hom.: 4

Bravo AF: 0.00341

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.82
DANN	Benign	0.51

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: rs3219198; hg19: chr6-160638193;