6-160224800-C-T

Variant names:

• chr6-160224800-C-T
• rs316003
• NM_003058.4:c.1506G>A

Variant summary

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

The NM_003058.4(SLC22A2):​c.1506G>A​(p.Val502Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,572,278 control chromosomes in the GnomAD database, including 459,886 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 0.70 (39330 hom., cov: 32)
  • Exomes 𝑓: 0.77 (420556 hom.)
• Consequence: SLC22A2 NM_003058.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• Publications: 37 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.805 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.1506G>A	p.Val502Val	synonymous	Exon 10 of 11	NP_003049.2	O15244-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.1506G>A	p.Val502Val	synonymous	Exon 10 of 11	ENSP00000355920.3	O15244-1
	SLC22A2	ENST00000486916.5	TSL:3	n.545G>A		non_coding_transcript_exon	Exon 5 of 6
	SLC22A2	ENST00000491092.1	TSL:5	n.1403G>A		non_coding_transcript_exon	Exon 9 of 10

Frequencies

GnomAD3 genomes AF: 0.704 AC: 106920 AN: 151968 Hom.: 39308 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.839

Gnomad AMR AF: 0.816

Gnomad ASJ AF: 0.793

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.790

Gnomad FIN AF: 0.847

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.728

GnomAD2 exomes AF: 0.776 AC: 185325 AN: 238764 AF XY: 0.780

Gnomad AFR exome AF: 0.462

Gnomad AMR exome AF: 0.886

Gnomad ASJ exome AF: 0.792

Gnomad EAS exome AF: 0.799

Gnomad FIN exome AF: 0.838

Gnomad NFE exome AF: 0.770

Gnomad OTH exome AF: 0.782

GnomAD4 exome AF: 0.767 AC: 1088868 AN: 1420192 Hom.: 420556 Cov.: 28 AF XY: 0.769 AC XY: 543246 AN XY: 706662

African (AFR) AF: 0.454 AC: 14723 AN: 32402

American (AMR) AF: 0.875 AC: 36889 AN: 42148

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 20052 AN: 25332

East Asian (EAS) AF: 0.821 AC: 31633 AN: 38546

South Asian (SAS) AF: 0.781 AC: 62538 AN: 80070

European-Finnish (FIN) AF: 0.836 AC: 43574 AN: 52144

Middle Eastern (MID) AF: 0.752 AC: 4244 AN: 5646

European-Non Finnish (NFE) AF: 0.766 AC: 831203 AN: 1085544

Other (OTH) AF: 0.754 AC: 44012 AN: 58360

GnomAD4 genome AF: 0.703 AC: 106983 AN: 152086 Hom.: 39330 Cov.: 32 AF XY: 0.711 AC XY: 52859 AN XY: 74364

African (AFR) AF: 0.473 AC: 19589 AN: 41436

American (AMR) AF: 0.817 AC: 12471 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.793 AC: 2755 AN: 3472

East Asian (EAS) AF: 0.800 AC: 4134 AN: 5170

South Asian (SAS) AF: 0.791 AC: 3815 AN: 4826

European-Finnish (FIN) AF: 0.847 AC: 8960 AN: 10584

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.776 AC: 52752 AN: 68008

Other (OTH) AF: 0.731 AC: 1545 AN: 2114

Alfa AF: 0.753 Hom.: 154433

Bravo AF: 0.692

Asia WGS AF: 0.796 AC: 2769 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.51
DANN	Benign	0.55
PhyloP100		-0.092
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: rs316003; hg19: chr6-160645832; COSMIC: COSV65269047;