rs316019

Variant names:

• chr6-160249250-A-C
• rs316019
• NM_003058.4:c.808T>G

Your query was ambiguous. Multiple possible variants found:

• chr6-160249250-A-C
• chr6-160249250-A-G
• chr6-160249250-A-T

Variant summary

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

The NM_003058.4(SLC22A2):​c.808T>G​(p.Ser270Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,605,228 control chromosomes in the GnomAD database, including 644,774 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.89 (60187 hom., cov: 33)
  • Exomes 𝑓: 0.90 (584587 hom.)
• Consequence: SLC22A2 NM_003058.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.50
• Publications: 274 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 (MetaRNN=3.5864516E-6).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A2	NM_003058.4	c.808T>G	p.Ser270Ala	missense_variant	Exon 4 of 11	ENST00000366953.8	NP_003049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A2	ENST00000366953.8	c.808T>G	p.Ser270Ala	missense_variant	Exon 4 of 11	1	NM_003058.4	ENSP00000355920.3
SLC22A2	ENST00000366952.1	c.745T>G	p.Ser249Ala	missense_variant	Exon 6 of 8	5		ENSP00000355919.1
SLC22A2	ENST00000491092.1	n.705T>G		non_coding_transcript_exon_variant	Exon 3 of 10	5

Frequencies

GnomAD3 genomes AF: 0.888 AC: 135119 AN: 152146 Hom.: 60117 Cov.: 33

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.899

Gnomad AMR AF: 0.917

Gnomad ASJ AF: 0.854

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.876

Gnomad FIN AF: 0.941

Gnomad MID AF: 0.832

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.887

GnomAD2 exomes AF: 0.898 AC: 219538 AN: 244340 AF XY: 0.898

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.948

Gnomad ASJ exome AF: 0.853

Gnomad EAS exome AF: 0.873

Gnomad FIN exome AF: 0.941

Gnomad NFE exome AF: 0.898

Gnomad OTH exome AF: 0.895

GnomAD4 exome AF: 0.897 AC: 1302811 AN: 1452964 Hom.: 584587 Cov.: 35 AF XY: 0.896 AC XY: 647892 AN XY: 722780

African (AFR) AF: 0.849 AC: 28061 AN: 33064

American (AMR) AF: 0.944 AC: 40535 AN: 42954

Ashkenazi Jewish (ASJ) AF: 0.855 AC: 22188 AN: 25962

East Asian (EAS) AF: 0.880 AC: 34640 AN: 39358

South Asian (SAS) AF: 0.874 AC: 73759 AN: 84346

European-Finnish (FIN) AF: 0.936 AC: 49991 AN: 53384

Middle Eastern (MID) AF: 0.875 AC: 5026 AN: 5742

European-Non Finnish (NFE) AF: 0.898 AC: 995271 AN: 1108066

Other (OTH) AF: 0.888 AC: 53340 AN: 60088

GnomAD4 genome AF: 0.888 AC: 135250 AN: 152264 Hom.: 60187 Cov.: 33 AF XY: 0.890 AC XY: 66276 AN XY: 74444

African (AFR) AF: 0.849 AC: 35239 AN: 41516

American (AMR) AF: 0.917 AC: 14045 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.854 AC: 2962 AN: 3470

East Asian (EAS) AF: 0.871 AC: 4512 AN: 5182

South Asian (SAS) AF: 0.877 AC: 4229 AN: 4820

European-Finnish (FIN) AF: 0.941 AC: 9980 AN: 10610

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.901 AC: 61336 AN: 68038

Other (OTH) AF: 0.890 AC: 1883 AN: 2116

Alfa AF: 0.894 Hom.: 298429

Bravo AF: 0.885

TwinsUK AF: 0.898 AC: 3331

ALSPAC AF: 0.890 AC: 3430

ESP6500AA AF: 0.854 AC: 3762

ESP6500EA AF: 0.892 AC: 7672

ExAC AF: 0.893 AC: 108454

Asia WGS AF: 0.895 AC: 3114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	17
DANN	Benign	0.93
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.35	T;T
MetaRNN	Benign	0.0000036	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M;.
PhyloP100		2.5
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.14
Sift	Uncertain	0.022	D;D
Sift4G	Uncertain	0.033	D;T
Polyphen		0.25	B;.
Vest4		0.078
MPC		0.19
ClinPred		0.036	T
GERP RS		-2.3
Varity_R		0.18
gMVP		0.72
Mutation Taster		=99/1	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: rs316019; hg19: chr6-160670282; COSMIC: COSV65266580; COSMIC: COSV65266580;