6-160216943-T-G

Position:

• chr6-160216943-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000366953.8(SLC22A2):​c.*489A>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 0.717 in 151,916 control chromosomes in the GnomAD database, including 40,652 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 0.72 (40652 hom., cov: 32)
  • Exomes 𝑓: 0.80 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC22A2 ENST00000366953.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.*489A>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.*489A>C		3_prime_UTR_variant	11/11	1	NM_003058.4	ENSP00000355920	P1
SLC22A2	ENST00000486916.5	n.640+7762A>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108914 AN: 151798 Hom.: 40622 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.742

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.803 AC: 61 AN: 76 Hom.: 24 Cov.: 0 AF XY: 0.900 AC XY: 36 AN XY: 40

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.767

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.717 AC: 108991 AN: 151916 Hom.: 40652 Cov.: 32 AF XY: 0.725 AC XY: 53846 AN XY: 74224

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.824

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.829

Gnomad4 SAS AF: 0.782

Gnomad4 FIN AF: 0.836

Gnomad4 NFE AF: 0.781

Gnomad4 OTH AF: 0.746

Alfa AF: 0.778 Hom.: 88349

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.68

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: rs2450975; hg19: chr6-160637975;