6-160243653-G-A

Variant names:

• chr6-160243653-G-A
• rs8177516
• NM_003058.4:c.1198C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_003058.4(SLC22A2):​c.1198C>T​(p.Arg400Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000835 in 1,613,962 control chromosomes in the GnomAD database, including 6 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 0.0043 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00048 (4 hom.)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.77
• Publications: 40 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.021221578).
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.1198C>T	p.Arg400Cys	missense	Exon 7 of 11	NP_003049.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.1198C>T	p.Arg400Cys	missense	Exon 7 of 11	ENSP00000355920.3
	SLC22A2	ENST00000486916.5	TSL:3	n.237C>T		non_coding_transcript_exon	Exon 2 of 6
	SLC22A2	ENST00000491092.1	TSL:5	n.1095C>T		non_coding_transcript_exon	Exon 6 of 10

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 650 AN: 152046 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0146

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00150

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.00123 AC: 309 AN: 251316 AF XY: 0.00102

Gnomad AFR exome AF: 0.0159

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000475 AC: 695 AN: 1461796 Hom.: 4 Cov.: 31 AF XY: 0.000415 AC XY: 302 AN XY: 727206

African (AFR) AF: 0.0148 AC: 494 AN: 33470

American (AMR) AF: 0.000962 AC: 43 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0000558 AC: 62 AN: 1111940

Other (OTH) AF: 0.00113 AC: 68 AN: 60392

GnomAD4 genome AF: 0.00429 AC: 653 AN: 152166 Hom.: 2 Cov.: 32 AF XY: 0.00415 AC XY: 309 AN XY: 74392

African (AFR) AF: 0.0146 AC: 607 AN: 41506

American (AMR) AF: 0.00150 AC: 23 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000206 AC: 14 AN: 67994

Other (OTH) AF: 0.00379 AC: 8 AN: 2110

Alfa AF: 0.00167 Hom.: 8

Bravo AF: 0.00488

ESP6500AA AF: 0.0148 AC: 65

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00146 AC: 177

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	24
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.77	D
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	D
MetaRNN	Benign	0.021	T
MetaSVM	Uncertain	0.0010	D
MutationAssessor	Pathogenic	3.5	M
PhyloP100		6.8
PrimateAI	Uncertain	0.57	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Uncertain	0.40
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.020	D
Polyphen		0.99	D
Vest4		0.93
MVP		0.82
MPC		0.30
ClinPred		0.088	T
GERP RS		5.5
Varity_R		0.73
gMVP		0.83
Mutation Taster		=74/26	polymorphism

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: rs8177516; hg19: chr6-160664685; COSMIC: COSV106509921; COSMIC: COSV106509921;