rs316019

chr6-160249250-A-Cchr6-160249250-A-T

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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 -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/exons	MANE	UniProt
SLC22A2	NM_003058.4	c.808T>G	p.Ser270Ala	missense_variant	4/11	ENST00000366953.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A2	ENST00000366953.8	c.808T>G	p.Ser270Ala	missense_variant	4/11	1	NM_003058.4	P1
SLC22A2	ENST00000366952.1	c.745T>G	p.Ser249Ala	missense_variant	6/8	5
SLC22A2	ENST00000491092.1	n.705T>G		non_coding_transcript_exon_variant	3/10	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

GnomAD3 exomes AF: 0.898 AC: 219538 AN: 244340 Hom.: 98818 AF XY: 0.898 AC XY: 118608 AN XY: 132122

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 SAS exome AF: 0.875

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

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.944

Gnomad4 ASJ exome AF: 0.855

Gnomad4 EAS exome AF: 0.880

Gnomad4 SAS exome AF: 0.874

Gnomad4 FIN exome AF: 0.936

Gnomad4 NFE exome AF: 0.898

Gnomad4 OTH exome AF: 0.888

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

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.917

Gnomad4 ASJ AF: 0.854

Gnomad4 EAS AF: 0.871

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.941

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.890

Alfa AF: 0.896 Hom.: 156017

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;.
MutationTaster	Benign	1.0	P;P
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

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: rs316019; hg19: chr6-160670282; COSMIC: COSV65266580; COSMIC: COSV65266580;