6-160243648-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_003058.4(SLC22A2):c.1203C>T(p.Ile401=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,614,012 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0033 (10 hom.)
• Consequence: SLC22A2 NM_003058.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.76

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 6-160243648-G-A is Benign according to our data. Variant chr6-160243648-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2657109.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.76 with no splicing effect.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A2	NM_003058.4	c.1203C>T	p.Ile401=	synonymous_variant	7/11	ENST00000366953.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A2	ENST00000366953.8	c.1203C>T	p.Ile401=	synonymous_variant	7/11	1	NM_003058.4	P1
SLC22A2	ENST00000486916.5	n.242C>T		non_coding_transcript_exon_variant	2/6	3
SLC22A2	ENST00000491092.1	n.1100C>T		non_coding_transcript_exon_variant	6/10	5

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 384 AN: 152092 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000652

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00432

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000660

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00274 AC: 689 AN: 251298 Hom.: 3 AF XY: 0.00290 AC XY: 394 AN XY: 135806

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00237

Gnomad ASJ exome AF: 0.00466

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000588

Gnomad FIN exome AF: 0.000601

Gnomad NFE exome AF: 0.00440

Gnomad OTH exome AF: 0.00293

GnomAD4 exome AF: 0.00326 AC: 4760 AN: 1461802 Hom.: 10 Cov.: 31 AF XY: 0.00329 AC XY: 2394 AN XY: 727214

Gnomad4 AFR exome AF: 0.000418

Gnomad4 AMR exome AF: 0.00266

Gnomad4 ASJ exome AF: 0.00532

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000638

Gnomad4 FIN exome AF: 0.000955

Gnomad4 NFE exome AF: 0.00377

Gnomad4 OTH exome AF: 0.00265

GnomAD4 genome AF: 0.00252 AC: 384 AN: 152210 Hom.: 3 Cov.: 32 AF XY: 0.00243 AC XY: 181 AN XY: 74412

Gnomad4 AFR AF: 0.000650

Gnomad4 AMR AF: 0.00190

Gnomad4 ASJ AF: 0.00432

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.000660

Gnomad4 NFE AF: 0.00441

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00396 Hom.: 1

Bravo AF: 0.00237

EpiCase AF: 0.00545

EpiControl AF: 0.00522

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

SLC22A2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.0050
Dann	Benign	0.52

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: rs8177515; hg19: chr6-160664680; COSMIC: COSV65265922; COSMIC: COSV65265922;