6-160217170-GA-GAA

Variant names:

• chr6-160217170-G-GA
• rs4646240
• NM_003058.4:c.*261dupT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_003058.4(SLC22A2):​c.*261dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00705 in 341,356 control chromosomes in the GnomAD database, including 37 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.013 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (5 hom.)
• Consequence: SLC22A2 NM_003058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

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.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0131 (1991/151738) while in subpopulation AFR AF= 0.0452 (1870/41380). AF 95% confidence interval is 0.0435. There are 32 homozygotes in gnomad4. There are 946 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.*261dupT		3_prime_UTR_variant	Exon 11 of 11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953	c.*261dupT		3_prime_UTR_variant	Exon 11 of 11	1	NM_003058.4	ENSP00000355920.3
SLC22A2	ENST00000498556.1	n.578dupT		non_coding_transcript_exon_variant	Exon 3 of 3	5
SLC22A2	ENST00000486916.5	n.640+7534dupT		intron_variant	Intron 5 of 5	3

Frequencies

GnomAD3 genomes AF: 0.0131 AC: 1985 AN: 151624 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0452

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00447

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000949

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.00771

GnomAD4 exome AF: 0.00219 AC: 416 AN: 189618 Hom.: 5 Cov.: 0 AF XY: 0.00198 AC XY: 191 AN XY: 96402

Gnomad4 AFR exome AF: 0.0378

Gnomad4 AMR exome AF: 0.00376

Gnomad4 ASJ exome AF: 0.000270

Gnomad4 EAS exome AF: 0.000345

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.000136

Gnomad4 NFE exome AF: 0.000692

Gnomad4 OTH exome AF: 0.00611

GnomAD4 genome AF: 0.0131 AC: 1991 AN: 151738 Hom.: 32 Cov.: 32 AF XY: 0.0128 AC XY: 946 AN XY: 74152

Gnomad4 AFR AF: 0.0452

Gnomad4 AMR AF: 0.00447

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.000581

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000949

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00763

Bravo AF: 0.0141

Asia WGS AF: 0.00260 AC: 9 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs4646240; hg19: chr6-160638202;